CN107540600A - A kind of recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid - Google Patents
A kind of recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid Download PDFInfo
- Publication number
- CN107540600A CN107540600A CN201610489313.7A CN201610489313A CN107540600A CN 107540600 A CN107540600 A CN 107540600A CN 201610489313 A CN201610489313 A CN 201610489313A CN 107540600 A CN107540600 A CN 107540600A
- Authority
- CN
- China
- Prior art keywords
- waste liquid
- formic acid
- avm hereinafter
- hereinafter batan
- recoverying
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000007788 liquid Substances 0.000 title claims abstract description 43
- 239000002699 waste material Substances 0.000 title claims abstract description 38
- 238000000034 method Methods 0.000 title claims abstract description 31
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 26
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 54
- 235000019253 formic acid Nutrition 0.000 claims abstract description 26
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims abstract description 25
- 150000001875 compounds Chemical class 0.000 claims abstract description 25
- 239000000706 filtrate Substances 0.000 claims abstract description 14
- -1 benzyloxy imino piperidines Chemical class 0.000 claims abstract description 13
- 230000003647 oxidation Effects 0.000 claims abstract description 8
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 8
- 238000002425 crystallisation Methods 0.000 claims abstract description 6
- 230000008025 crystallization Effects 0.000 claims abstract description 6
- 239000007787 solid Substances 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 87
- 238000006243 chemical reaction Methods 0.000 claims description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 13
- 239000012074 organic phase Substances 0.000 claims description 13
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
- 230000001590 oxidative effect Effects 0.000 claims description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 10
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 9
- DOVQCCKNWBBMMQ-UHFFFAOYSA-N C(C1=CC=CC=C1)OC1CCC(NC1)=N Chemical class C(C1=CC=CC=C1)OC1CCC(NC1)=N DOVQCCKNWBBMMQ-UHFFFAOYSA-N 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 8
- 239000008346 aqueous phase Substances 0.000 claims description 8
- 239000003638 chemical reducing agent Substances 0.000 claims description 6
- 150000007529 inorganic bases Chemical class 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- 239000011591 potassium Substances 0.000 claims description 6
- 229910052700 potassium Inorganic materials 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 5
- 239000012279 sodium borohydride Substances 0.000 claims description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 4
- 238000006386 neutralization reaction Methods 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 235000006408 oxalic acid Nutrition 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 claims description 3
- 229910010277 boron hydride Inorganic materials 0.000 claims description 2
- NKWPZUCBCARRDP-UHFFFAOYSA-L calcium bicarbonate Chemical compound [Ca+2].OC([O-])=O.OC([O-])=O NKWPZUCBCARRDP-UHFFFAOYSA-L 0.000 claims description 2
- 229910000020 calcium bicarbonate Inorganic materials 0.000 claims description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 2
- KWZWNVAHEQHCTQ-UHFFFAOYSA-N diacetyloxyboranyl acetate Chemical compound CC(=O)OB(OC(C)=O)OC(C)=O KWZWNVAHEQHCTQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- BWILYWWHXDGKQA-UHFFFAOYSA-M potassium propanoate Chemical compound [K+].CCC([O-])=O BWILYWWHXDGKQA-UHFFFAOYSA-M 0.000 claims description 2
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 10
- LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 abstract description 6
- 238000011084 recovery Methods 0.000 abstract description 6
- 230000007613 environmental effect Effects 0.000 abstract description 3
- 150000002148 esters Chemical class 0.000 abstract description 3
- 230000000977 initiatory effect Effects 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- ISENTNSFZWHPJB-UHFFFAOYSA-N 2-phenylmethoxypiperidin-1-amine Chemical compound C(C1=CC=CC=C1)OC1N(CCCC1)N ISENTNSFZWHPJB-UHFFFAOYSA-N 0.000 abstract 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 abstract 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 238000009835 boiling Methods 0.000 description 9
- 239000012065 filter cake Substances 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000010410 layer Substances 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 5
- 238000004064 recycling Methods 0.000 description 5
- 238000005292 vacuum distillation Methods 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000004296 chiral HPLC Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000004519 grease Substances 0.000 description 3
- 150000003891 oxalate salts Chemical class 0.000 description 3
- GEVPUGOOGXGPIO-UHFFFAOYSA-N oxalic acid;dihydrate Chemical class O.O.OC(=O)C(O)=O GEVPUGOOGXGPIO-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000000171 quenching effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- LLSKXGRDUPMXLC-UHFFFAOYSA-N 1-phenylpiperidine Chemical class C1CCCCN1C1=CC=CC=C1 LLSKXGRDUPMXLC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 108090000204 Dipeptidase 1 Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical class ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 102000006635 beta-lactamase Human genes 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007033 dehydrochlorination reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- DKGAVHZHDRPRBM-UHFFFAOYSA-N tert-butyl alcohol Substances CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Hydrogenated Pyridines (AREA)
Abstract
The present invention relates to a kind of recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid, using caused waste liquid in AVM hereinafter Batan intermediate 5R benzyloxy amino piperidine 2S formic acid ester oxalate IIb production processes as initiation material, 5 benzyloxy imino piperidines 2S formic acid esters III are generated through peroxidating, the chosen property reduction of III, chiral crystallization split, are filtrated to get solid 5R benzyloxy amino piperidine 2S formic acid ester oxalate IIb, and gained filtrate repeats above oxidation, reduction, split process.The neutralized preparation 5R benzyloxies amino piperidine 2S formic acid esters IIa of compound IIb, AVM hereinafter Batan I can be prepared using gained compound IIa or compound IIb.The present invention is easy to operate, improves atom utilization, the final total recoverys of compound IIb advantageously reduce cost, advantageously reduce the waste liquid of AVM hereinafter Batan, be advantageous to environmental protection up to more than 99.0%.
Description
Technical field
The present invention relates to a kind of recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid, especially one kind is by AVM hereinafter bar
Smooth intermediate waste liquid prepares 5R- benzyloxy amino piperidine -2S- formic acid esters (IIa) and 5R- benzyloxy amino piperidine -2S- formic acid esters oxalic acid
The method of salt (IIb), belongs to medicine bioengineering chemical field.
Background technology
AVM hereinafter Batan has broad spectrum antibiotic activity, when being used in combination with all kinds of cephalos and carbapenem antibiotics, can suppress A
The beta-lactamase of type (including ESBL and KPC) and c-type, to the Escherichia coli containing extended spectrumβ-lactamase and the primary lung of Cray
Scorching bacillus, the Escherichia coli containing excess AmpC enzymes and the Escherichia coli simultaneously containing AmpC and extended spectrumβ-lactamase
With remarkable activity.No. CAS of AVM hereinafter Batan (I) is 1192491-61-4, and chemical name is [(1R, 2S, 5R) -2- (amino carbonyls
Base) -7- oxos -1,6- diazabicyclo [3.2.1] octyl- 6- yls] sodium sulphate, structural formula such as following formula I：
5R- benzyloxy amino piperidine -2S- formic acid esters (IIa) and 5R- benzyloxy amino piperidine -2S- formic acid ester oxalates (IIb)
It is the key intermediate for preparing AVM hereinafter Batan.Patent document WO2012172368, US2010197928, US2013012712 are reported
The synthetic method of 5R- benzyloxy amino piperidine -2S- formic acid esters, referring to reaction scheme 1.Using the L-Glutimic acid ester of N-protected as
Initiation material, prepared through Trimethylsulfoxonium Iodide open loop, benzyloxy amine and carbonyl condensation and N- guarantors are sloughed under corresponding imines, acid condition
The cyclization of intramolecular dehydrochlorination, selective reduction, chiral resolution obtain the neutralized system of product I Ib, IIb under shield base, alkalescence condition
Standby IIa.
The L-Glutimic acid ester and Trimethylsulfoxonium Iodide price of the raw materials used N-protected of this method are higher, and selectively
Reduction obtains two kinds of enantiomter 5R- benzyloxies amino piperidine -2S- formic acid esters and 5S- benzyloxy amino piperidine -2S- formic acid esters
Ratio is 3:1, there was only 65% by the compound III yields for obtaining product I Ib through reduction, chiral resolution, contain 35% in filtrate
The enantiomter of total amount, the wherein ratio of 5R- benzyloxies amino piperidine -2S- formic acid esters and 5S- benzyloxy amino piperidine -2S- formic acid esters
Example is 2:5, atom utilization is low.Simultaneous reactions process needs to protect, is deprotected, and operation requires high and cumbersome, and solvent uses
Amount is big, and " three wastes " discharge is big, and atom utilization is low, is unfavorable for environmental protection.
The content of the invention
In view of the shortcomings of the prior art, the present invention provides a kind of recycling side of AVM hereinafter Batan intermediate production waste liquid
Method, the production waste liquid especially with AVM hereinafter Batan intermediate 5R- benzyloxy amino piperidine -2S- formic acid ester oxalates (IIb) (contain
Have 5S- benzyloxy amino piperidine -2S- formic acid ester oxalates or (5S, 5R)-benzyloxy amino piperidine of different enantiomter ratios -
The filtrate of 2S- formic acid ester oxalates) prepare 5R- benzyloxy amino piperidine -2S- formic acid esters (IIa) and 5R- benzyloxy amino piperidines -2S-
Formic acid ester oxalate (IIb), the recycling of AVM hereinafter Batan intermediate production waste liquid is realized, improves atom utilization, and solve
The problem of " three wastes " discharge is big.
Term explanation：
AVM hereinafter Batan intermediate waste liquid：Refer in 5R- benzyloxy amino piperidine -2S- formic acid ester oxalate (IIb) production process
Caused waste liquid.
Containing 5S- benzyloxy amino piperidine -2S- formic acid ester oxalates (IIb) or different enantiomter ratios in waste liquid
(5S, 5R)-benzyloxy amino piperidine -2S- formic acid ester oxalates.Compound IIb production process is this area routine techniques.
Compound IIb：5R- benzyloxy amino piperidine -2S- formic acid ester oxalates (IIb).
Compound IIa：5R- benzyloxy amino piperidine -2S- formic acid esters (IIa).
Compound III：5- benzyloxy imino piperidines -2S- formic acid esters (III).
Compound number and formula numbers in this specification is completely the same, and there is identical to refer to relation.
Technical scheme is as follows：
A kind of recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid, comprises the following steps：
(1) oxidizing AVM hereinafter Batan intermediate waste liquid is utilized, is allowed to be converted into compound III：5- benzyloxy iminos
Piperidines -2S- formic acid esters；
(2) the chosen property reduction of compound III, chiral crystallization split, filtered, and obtain compound IIb：Solid 5R- benzyloxies
Amino piperidine -2S- formic acid ester oxalates；
Filtrate repeats above oxidation, reduction, split process.
Compound IIb is solid salt in the present invention, filtered to obtain, and the Solid-state Optics purity is high, can meet to use, and is walked
Suddenly the yield of (2) is 65% or so.The raw material for having about 35% is converted into (5S, 5R)-benzyloxy ammonia of different enantiomter ratios
Phenylpiperidines -2S- formic acid ester oxalates, are present in filtrate, can not effectively be utilized because its optical purity is unqualified, cause waste material
More, atom utilization is low., can be by (5S, 5R)-benzyloxy amino piperazine of different enantiomter ratios using the method for the present invention
Pyridine -2S- formic acid ester oxalates prepare the compound IIb of high-optical-purity, and in production, the step filtrate is through being repeated several times above oxygen
Change, reduce, split process, compound IIb final utilization rate is close to quantifying, and total recovery is up to more than 99.0%.
The reaction equation of the present invention is following (reaction scheme 2)：
Can be by 5R- benzyloxy amino piperidine -2S- formic acid esters (IIa) or 5R- benzyloxy amino piperidine -2S- formic acid obtained by the present invention
Ester oxalate (IIb) prepares AVM hereinafter Batan (I) according to known methods, and reaction equation is following (reaction scheme 3)：
In more detail, a kind of recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid, step are as follows：
(1) AVM hereinafter Batan intermediate waste liquid is distilled, reclaims ethyl acetate and methanol, then adds organic solvent, inorganic base
After the aqueous solution neutralizes, aqueous phase is separated, obtains organic phase；Oxidant is added into organic phase, aoxidizes 5S- benzyloxy amino piperidine -2S- first
Acid esters and 5R- benzyloxy amino piperidine -2S- formic acid esters enantiomters, are allowed to be converted into 5- benzyloxy imino piperidines -2S- formic acid
Ester (III)；
(2) compound III is in the presence of the 95-98wt% concentrated sulfuric acids, in ethyl acetate, is reduced through reducing agent, adds grass
Acid, chiral crystallization are split, filtering, obtain 5R- benzyloxy amino piperidine -2S- formic acid ester oxalates (IIb)；Step (2) filtrate weighs again
Oxidation more than multiple, reduction, split process.
, according to the invention it is preferred to, also comprise the following steps (3)：
(3) compound IIb is dissolved in solvent, neutralizes to obtain compound IIa through alkali：5R- benzyloxy amino piperidine -2S- formic acid
Ester,
, according to the invention it is preferred to, step (1) described organic solvent be dichloromethane, chloroform, 1,2- dichloroethanes, benzene,
The mass ratio of toluene or its mixture, the solvent and waste liquid used is 0.1:1 to 1:1.
, according to the invention it is preferred to, step (1) described inorganic base aqueous solution be wet chemical, aqueous sodium carbonate,
Potassium bicarbonate aqueous solution, sodium bicarbonate aqueous solution or/and ammoniacal liquor；Inorganic base total amount and contained enantiomter (5R, 5S)-benzyloxy
The mol ratio of amino piperidine -2S- formic acid ester oxalate total amounts is (1.5-3.0):1.
, according to the invention it is preferred to, step (1) the neutralization reaction temperature is 10-40 DEG C, and the reaction time is 2-5 hours.
, according to the invention it is preferred to, the oxidant used in step (1) described oxidation is hydrogen peroxide or tert-butyl hydroperoxide
The mol ratio of hydrogen, oxidant and contained enantiomter (5R, 5S)-benzyloxy amino piperidine -2S- formic acid ester oxalate total amounts is
(1.0-2.0)：1, the oxidizing reaction temperature is 0-60 DEG C, reacts 2-6 hours.
, according to the invention it is preferred to, the mol ratio of step (2) concentrated sulfuric acid and compound III is (3.0-6.0)：1,
Step (2) ethyl acetate and compound III mass ratio are 5:1 to 20:1.
, according to the invention it is preferred to, step (2) described reducing agent is sodium borohydride, tricyano sodium borohydride, triacetyl oxygen
Base sodium borohydride, three propionyloxy sodium borohydrides, potassium borohydride, tricyano potassium borohydride, triacetoxy boron hydride potassium or/and
Three propionyloxy potassium borohydrides, the mol ratio of the reducing agent and compound III is (2.0-4.0)：1.
, according to the invention it is preferred to, step (3) described solvent is ethyl acetate, dichloromethane, chloroform, the chloroethenes of 1,2- bis-
Alkane, benzene or/and toluene, the solvent and compound IIb mass ratio are 4:1 to 12:1.
, according to the invention it is preferred to, step (3) described alkali can be potassium carbonate, sodium carbonate, calcium carbonate, saleratus, carbonic acid
The mixture of hydrogen sodium, calcium bicarbonate, ammoniacal liquor or more alkali；Alkali and compound IIb mol ratio are (1.5-3.0):1.
, according to the invention it is preferred to, in step (3), the neutralization reaction temperature is 10-40 DEG C, and the reaction time is that 2-5 is small
When.
The technical characterstic and excellent results of the present invention：
1st, the present invention is recycled for AVM hereinafter Batan intermediate production waste liquid, utilizes oxidizing AVM hereinafter Batan
Caused waste liquid in intermediate 5R- benzyloxy amino piperidine -2S- formic acid ester oxalate production processes, is allowed to be converted into 5- benzyloxies
Imido phenylpiperidines -2S- formic acid esters (III), the chosen property reduction of compound III, chiral crystallization split, are filtrated to get solid 5R-
Benzyloxy amino piperidine -2S- formic acid ester oxalate (IIb), filtrate repeat above oxidation, reduction, split process, compound IIb
It is neutralized to obtain 5R- benzyloxy amino piperidine -2S- formic acid esters (IIa), it can prepare Ah using gained compound IIa or compound IIb
Tie up Batan (I).
2nd, the present invention utilizes short-cut method, makes AVM hereinafter Batan intermediate 5R- benzyloxy amino piperidine -2S- formic acid ester oxalates
Production waste liquid rationally utilized, improve atom utilization, compound IIb total recoverys are advantageous to up to more than 99.0%
Cost is reduced, advantageously reduces the three wastes and the environmental protection of AVM hereinafter Batan.
Embodiment
The present invention is described in detail with reference to embodiments, but the present invention is not only limited to this.
% in embodiment is mass percent, except having a special instruction.
The concentrated sulfuric acid used is the concentrated sulfuric acid that concentration is 95-98wt% in embodiment, and ammoniacal liquor is that concentration is 10-30wt%
Ammoniacal liquor.
Using gas phase or liquid chromatograph monitoring course of reaction and product purity, using equipped with chiral column (ES-OVS,
150mm × 4.6mm, Agilent company) liquid chromatograph detection optical purity (area is than %), and calculated yield and e.e%
Value.
Embodiment 1：5R- benzyloxy amino piperidine -2S- methyl formate oxalates (IIb1) preparation
To equipped with stirring, 500 grams of ethyl acetate being added in 2000 milliliters of four-hole boiling flasks of thermometer, 105.0g (0.4 is added
Mole) 5- benzyloxy imino piperidines -2S- methyl formates (III1).Kept for minus 20 DEG C to minus between 15 DEG C, be added dropwise 201.0 grams it is dense
Sulfuric acid (2.0 moles), drop finish, and stir 1 hour.
At minus 20 DEG C, 190.0 grams of (0.9 mole) sodium triacetoxy borohydrides are added, -20 DEG C to -15 DEG C stirrings are anti-
Answer 5 hours.Below 0 DEG C of keeping temperature, add 200 grams of water quenchings and go out reaction；It is 7-8 to be neutralized to system pH with ammoniacal liquor.Layering, use
Saturated common salt water washing organic layer twice, 100 grams every time.Organic phase concentration and recovery solvent, is then added into gained residue
320 grams of ethyl acetate, 160 grams of methanol, 52.0 grams of (0.42 mole) oxalic acid dihydrates, 45 DEG C are heated to, after stirring 2 hours,
Cooling, filtering.100 grams of ethyl acetate/methanols (2 of filter cake:1) mixed liquor washing filter cake, then washed with 50 grams of ethyl acetate, is closed
And all filtrates, the enantiomter containing 35.3% integral molar quantity, wherein 5R- benzyloxies amino piperidine -2S- formic acid esters in filtrate
Molar ratio with 5S- benzyloxy amino piperidine -2S- formic acid esters is 2:5, for embodiment 4.Filter cake is dried in vacuo, and obtains 91.6
Gram individual isomer 5R- benzyloxy amino piperidine -2S- methyl formate oxalates, chiral HPLC purity 99.3%, yield are
64.7%.
Embodiment 2：5R- benzyloxy amino piperidine -2S- Ethyl formate oxalates (IIb2) preparation
To equipped with stirring, 500 grams of ethyl acetate being added in 2000 milliliters of four-hole boiling flasks of thermometer, 110.0g (0.4 is added
Mole) 5- benzyloxy imino piperidines -2S- Ethyl formates (III2), for minus 20 DEG C of holding to minus between 15 DEG C, 201.0 grams of dropwise addition is dense
Sulfuric acid (2.0 moles), drop finish, and stir 1 hour.
At minus 20 DEG C, 190.0 grams of (0.9 mole) sodium triacetoxy borohydrides are added, -20 DEG C to -15 DEG C stirrings are anti-
Answer 5 hours.Below 0 DEG C of keeping temperature, add 200 grams of water quenchings and go out reaction；It is 7-8 to be neutralized to system pH with ammoniacal liquor.Layering, use
Saturated common salt water washing organic layer twice, 100 grams every time.Organic phase concentration and recovery solvent, is then added into gained residue
320 grams of ethyl acetate, 160 grams of methanol, 52.0 grams of (0.42 mole) oxalic acid dihydrates, 45 DEG C are heated to, after stirring 2 hours,
Cooling, filtering.100 grams of ethyl acetate/methanols (2 of filter cake:1) mixed liquor washing filter cake, then washed with 50 grams of ethyl acetate, is closed
And all filtrates, for embodiment 5.Filter cake is dried in vacuo, and obtains 96.3 grams of individual isomer 5R- benzyloxy amino piperidine -2S- first
Acetoacetic ester oxalates, chiral HPLC purity 99.6%, yield 65.4%.
Embodiment 3：5R- benzyloxy amino piperidine -2S- benzyl formate oxalates (IIb3) preparation
To equipped with stirring, 500 grams of ethyl acetate being added in 2000 milliliters of four-hole boiling flasks of thermometer, 135.0g (0.4 is added
Mole) 5- benzyloxy imino piperidines -2S- benzyl formates (III3), for minus 20 DEG C of holding to minus between 15 DEG C, 201.0 grams of dropwise addition is dense
Sulfuric acid (2.0 moles), drop finish, and stir 1 hour.
At minus 20 DEG C, 190.0 grams of (0.9 mole) sodium triacetoxy borohydrides are added, -20 DEG C to -15 DEG C stirrings are anti-
Answer 5 hours.Below 0 DEG C of keeping temperature, add 200 grams of water quenchings and go out reaction；It is 7-8 to be neutralized to system pH with ammoniacal liquor.Layering, use
Saturated common salt water washing organic layer twice, 100 grams every time.Organic phase concentration and recovery solvent, is then added into gained residue
320 grams of ethyl acetate, 160 grams of methanol, 52.0 grams of (0.42 mole) oxalic acid dihydrates, 45 DEG C are heated to, after stirring 2 hours,
Cooling, filtering.100 grams of ethyl acetate/methanols (2 of filter cake:1) mixed liquor washing filter cake, then washed with 50 grams of ethyl acetate, is closed
And all filtrates, for embodiment 6.Filter cake is dried in vacuo, and obtains 118.8 grams of individual isomer 5R- benzyloxy amino piperidines -2S-
Benzyl formate oxalates, chiral HPLC purity 99.7%, yield 69.0%.
Embodiment 4：5- benzyloxy imino piperidines -2S- methyl formates (III1) preparation
Into 2000 milliliters of glass flasks equipped with stirring, thermometer and distilling apparatus, add the gained of embodiment 1 and filter
Liquid, ethyl acetate, first alcohol and water are distilled out, gained residue is cooled to 0-5 DEG C, add 300 grams of 1,2- dichloroethanes, 140
Gram 10% sodium hydroxide, in 0-5 DEG C of stirring reaction 3 hours.Layering, aqueous phase are extracted with 1,2- dichloroethanes, 100 grams every time (extractions
Water layer after taking contains oxalates, for separately reclaiming), by the organic layer of merging be transferred to it is another with stirring, thermometer,
In 1000 milliliters of four-hole boiling flasks of constant pressure funnel, 25 gram of 30% hydrogen peroxide, 30-35 DEG C of stirring reaction 3 hours are added.Point
Layer, aqueous phase are extracted with 1,2- dichloroethanes, 50 grams every time, merge organic phase, and after being distilled to recover solvent, vacuum distillation obtains 36.5
Gram light yellow transparent liquid 5- benzyloxy imino piperidines -2S- methyl formates, GC purity 99.1%, yield 99.2%.
Embodiment 5：5- benzyloxy imino piperidines -2S- Ethyl formates (III2) preparation
Into 2000 milliliters of glass flasks equipped with stirring, thermometer and distilling apparatus, add the gained of embodiment 2 and filter
Liquid, ethyl acetate, first alcohol and water are distilled out, gained residue is cooled to 0-5 DEG C, add 300 grams of 1,2- dichloroethanes, 140
Gram 10% sodium hydroxide, in 0-5 DEG C of stirring reaction 3 hours.Layering, aqueous phase are extracted with 1,2- dichloroethanes, 100 grams every time (extractions
Water layer after taking contains oxalates, for separately reclaiming), by the organic layer of merging be transferred to it is another with stirring, thermometer,
In 1000 milliliters of four-hole boiling flasks of constant pressure funnel, 20.5 gram of 70% tertbutanol peroxide, 20-25 DEG C of stirring reaction 3 are added
Hour.Layering, aqueous phase are extracted with 1,2- dichloroethanes, 50 grams every time, merge organic phase, after being distilled to recover solvent, are evaporated under reduced pressure
37.5 grams of light yellow transparent liquid 5- benzyloxy imino piperidines -2S- Ethyl formates, GC purity 99.4% are obtained, yield is
98.3%.
Embodiment 6：5- benzyloxy imino piperidines -2S- benzyl formates (III3) preparation
Into 2000 milliliters of glass flasks equipped with stirring, thermometer and distilling apparatus, add the gained of embodiment 3 and filter
Liquid, ethyl acetate, first alcohol and water are distilled out, gained residue is cooled to 0-5 DEG C, add 400 grams of 1,2- dichloroethanes, 170
Gram 15% sodium carbonate, in 10-15 DEG C of stirring reaction 3 hours.Layering, aqueous phase are extracted with 1,2- dichloroethanes, 100 grams every time (extractions
Water layer after taking contains oxalates, for separately reclaiming), by the organic layer of merging be transferred to it is another with stirring, thermometer,
In 1000 milliliters of four-hole boiling flasks of constant pressure funnel, 27 gram of 30% hydrogen peroxide, 30-35 DEG C of stirring reaction 4 hours are added.Point
Layer, aqueous phase are extracted with 1,2- dichloroethanes, 50 grams every time, merge organic phase, and after being distilled to recover solvent, vacuum distillation obtains 46.5
Gram light yellow transparent liquid 5- benzyloxy imino piperidines -2S- benzyl formates, GC purity 99.3%, yield 98.5%.
Embodiment 7：5R- benzyloxy amino piperidine -2S- methyl formates (IIa1) preparation
To equipped with stirring, thermometer 500 milliliters of four-hole boiling flasks in add 300 grams of ethyl acetate, 42.5g (0.12 mole)
5R- benzyloxy amino piperidine -2S- methyl formate oxalates, the sodium bicarbonate solution of 100 grams of (0.24 moles) 20%, 30-35 DEG C is stirred
Mix reaction 2 hours.Layering, water layer are extracted twice with ethyl acetate, 60 grams every time.Merge organic layer, saturated nacl aqueous solution is washed
Wash twice, 50 grams every time.After gained organic phase recycling design, vacuum distillation obtains lurid stickiness grease 5R- benzyloxy ammonia
Phenylpiperidines -2S- methyl formates, GC purity 99.8%, yield 97.3%.
Embodiment 8：5R- benzyloxy amino piperidine -2S- Ethyl formates (IIa2) preparation
To equipped with stirring, thermometer 500 milliliters of four-hole boiling flasks in add 300 grams of ethyl acetate, 44.0g (0.12 mole)
5R- benzyloxy amino piperidine -2S- Ethyl formate oxalates, the sodium bicarbonate solution of 100 grams of (0.24 moles) 20%, 20-25 DEG C is stirred
Mix reaction 2 hours.Layering, water layer are extracted twice with ethyl acetate, 60 grams every time.Merge organic layer, saturated nacl aqueous solution is washed
Wash twice, 50 grams every time.After gained organic phase recycling design, vacuum distillation obtains lurid stickiness grease 5R- benzyloxy ammonia
Phenylpiperidines -2S- Ethyl formates, GC purity 99.5%, yield 96.8%.
Embodiment 9：5R- benzyloxy amino piperidine -2S- benzyl formates (IIa3) preparation
To equipped with stirring, thermometer 500 milliliters of four-hole boiling flasks in add 350 grams of ethyl acetate, 51.0g (0.12 mole)
5R- benzyloxy amino piperidine -2S- benzyl formate oxalates, the sodium bicarbonate solution of 100 grams of (0.24 moles) 20%, 30-35 DEG C is stirred
Mix reaction 3 hours.Layering, water layer are extracted twice with ethyl acetate, 100 grams every time.Merge organic layer, saturated nacl aqueous solution is washed
Wash twice, 50 grams every time.After gained organic phase recycling design, vacuum distillation obtains lurid stickiness grease 5R- benzyloxy ammonia
Phenylpiperidines -2S- benzyl formates, GC purity 99.6%, yield 96.5%.
Claims (10)
1. a kind of recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid, comprises the following steps：
(1) oxidizing AVM hereinafter Batan intermediate waste liquid is utilized, is allowed to be converted into compound III：5- benzyloxy iminos piperidines-
2S- formic acid esters；
(2) the chosen property reduction of compound III, chiral crystallization split, filtered, and obtain compound IIb：Solid 5R- benzyloxy amino
Piperidines -2S- formic acid ester oxalates；
Filtrate repeats above oxidation, reduction, split process.
2. the recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid according to claim 1, step are as follows：
(1) AVM hereinafter Batan intermediate waste liquid is distilled, reclaims ethyl acetate and methanol, it is water-soluble then to add organic solvent, inorganic base
After liquid neutralizes, aqueous phase is separated, obtains organic phase；Oxidant is added into organic phase, aoxidizes 5S- benzyloxy amino piperidine -2S- formic acid esters
With 5R- benzyloxy amino piperidine -2S- formic acid esters enantiomters, it is allowed to be converted into 5- benzyloxy imino piperidines -2S- formic acid esters
(III)；
(2) compound III is in the presence of the 95-98wt% concentrated sulfuric acids, in ethyl acetate, is reduced through reducing agent, adds oxalic acid, hand
Property crystallization split, filtering, obtain 5R- benzyloxy amino piperidine -2S- formic acid ester oxalates (IIb)；Step (2) filtrate repeat with
Upper oxidation, reduction, split process.
3. the recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid according to claim 2, it is characterised in that step
(1) organic solvent is dichloromethane, chloroform, 1,2- dichloroethanes, benzene or/and toluene；Preferably, the solvent with it is used
The mass ratio of waste liquid is 0.1:1 to 1:1.
4. the recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid according to claim 2, it is characterised in that step
(1) inorganic base aqueous solution is wet chemical, aqueous sodium carbonate, potassium bicarbonate aqueous solution, sodium bicarbonate aqueous solution
Or/and ammoniacal liquor；Preferably, inorganic base total amount and contained enantiomter (5R, 5S)-benzyloxy amino piperidine -2S- formic acid esters oxalic acid
The mol ratio of salt total amount is (1.5-3.0):1.
5. the recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid according to claim 2, it is characterised in that step
(1) the neutralization reaction temperature is 10-40 DEG C, and the reaction time is 2-5 hours.
6. the recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid according to claim 2, it is characterised in that step
(1) oxidant used in the oxidation is hydrogen peroxide or TBHP, oxidant and contained enantiomter (5R,
The mol ratio of 5S)-benzyloxy amino piperidine -2S- formic acid ester oxalate total amounts is (1.0-2.0)：1, the oxidizing reaction temperature is
0-60 DEG C, react 2-6 hours.
7. the recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid according to claim 2, it is characterised in that step
(2) mol ratio of the concentrated sulfuric acid and compound III is (3.0-6.0)：1, the quality of step (2) ethyl acetate and compound III
Than for 5:1 to 20:1.
8. the recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid according to claim 2, it is characterised in that step
(2) reducing agent be sodium borohydride, tricyano sodium borohydride, sodium triacetoxy borohydride, three propionyloxy sodium borohydrides,
Potassium borohydride, tricyano potassium borohydride, triacetoxy boron hydride potassium or/and three propionyloxy potassium borohydrides；Preferably, it is described
The mol ratio of reducing agent and compound III is (2.0-4.0)：1.
9. the recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid according to claim 1 or 2, in addition to following step
Suddenly (3)：
(3) compound IIb is dissolved in solvent, neutralizes to obtain compound IIa through alkali：5R- benzyloxy amino piperidine -2S- formic acid esters,
10. the recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid according to claim 9, it is characterised in that step
Suddenly (3) described solvent is ethyl acetate, dichloromethane, chloroform, 1,2- dichloroethanes, benzene or/and toluene；Preferably, it is described molten
Agent and compound IIb mass ratio are 4:1 to 12:1；
Preferably, the alkali can be potassium carbonate, sodium carbonate, calcium carbonate, saleratus, sodium acid carbonate, calcium bicarbonate, ammoniacal liquor or with
The mixture of upper alkali；Preferably, alkali and compound IIb mol ratio are (1.5-3.0):1；
Preferably, in step (3), the neutralization reaction temperature is 10-40 DEG C, and the reaction time is 2-5 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610489313.7A CN107540600B (en) | 2016-06-28 | 2016-06-28 | A kind of recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610489313.7A CN107540600B (en) | 2016-06-28 | 2016-06-28 | A kind of recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107540600A true CN107540600A (en) | 2018-01-05 |
| CN107540600B CN107540600B (en) | 2019-07-09 |
Family
ID=60962093
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610489313.7A Active CN107540600B (en) | 2016-06-28 | 2016-06-28 | A kind of recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107540600B (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107941969A (en) * | 2017-11-07 | 2018-04-20 | 中山奕安泰医药科技有限公司 | The detection method of 2 formamide of (2S, 5R) Atenolol phenylpiperidines |
| CN108373442A (en) * | 2018-03-29 | 2018-08-07 | 台州职业技术学院 | A kind of recovery method of AVM hereinafter Batan centre isomers |
| CN111072660A (en) * | 2018-10-22 | 2020-04-28 | 新发药业有限公司 | Simple preparation method of rilibatan |
| CN112250533A (en) * | 2020-10-22 | 2021-01-22 | 中山奕安泰医药科技有限公司 | Synthesis method of (S) -1- (3-ethoxy-4-methoxyphenyl) -2- (methylsulfonyl) ethylamine |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102056901A (en) * | 2007-09-14 | 2011-05-11 | 诺夫谢尔公司 | Method for preparing disubstituted piperidine and intermediates |
| CN103649051A (en) * | 2011-06-17 | 2014-03-19 | 阿斯利康(瑞典)有限公司 | Process for preparing heterocyclic compounds including trans-7-oxo-6-(sulphooxy)-1, 6-diazabicyclo[3,2,1]octane-2-carboxamide and salts thereof |
| CN105348173A (en) * | 2015-12-02 | 2016-02-24 | 中山奕安泰医药科技有限公司 | Method for synthesizing avibactam intermediate 5 through asymmetric catalytic hydrogenation method |
-
2016
- 2016-06-28 CN CN201610489313.7A patent/CN107540600B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102056901A (en) * | 2007-09-14 | 2011-05-11 | 诺夫谢尔公司 | Method for preparing disubstituted piperidine and intermediates |
| CN103649051A (en) * | 2011-06-17 | 2014-03-19 | 阿斯利康(瑞典)有限公司 | Process for preparing heterocyclic compounds including trans-7-oxo-6-(sulphooxy)-1, 6-diazabicyclo[3,2,1]octane-2-carboxamide and salts thereof |
| CN105348173A (en) * | 2015-12-02 | 2016-02-24 | 中山奕安泰医药科技有限公司 | Method for synthesizing avibactam intermediate 5 through asymmetric catalytic hydrogenation method |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107941969A (en) * | 2017-11-07 | 2018-04-20 | 中山奕安泰医药科技有限公司 | The detection method of 2 formamide of (2S, 5R) Atenolol phenylpiperidines |
| CN108373442A (en) * | 2018-03-29 | 2018-08-07 | 台州职业技术学院 | A kind of recovery method of AVM hereinafter Batan centre isomers |
| CN108373442B (en) * | 2018-03-29 | 2020-07-03 | 台州职业技术学院 | Method for recovering abamectin intermediate isomer |
| CN111072660A (en) * | 2018-10-22 | 2020-04-28 | 新发药业有限公司 | Simple preparation method of rilibatan |
| CN111072660B (en) * | 2018-10-22 | 2021-05-18 | 新发药业有限公司 | Simple preparation method of rilibatan |
| CN112250533A (en) * | 2020-10-22 | 2021-01-22 | 中山奕安泰医药科技有限公司 | Synthesis method of (S) -1- (3-ethoxy-4-methoxyphenyl) -2- (methylsulfonyl) ethylamine |
| CN112250533B (en) * | 2020-10-22 | 2022-03-22 | 中山奕安泰医药科技有限公司 | Synthesis method of (S) -1- (3-ethoxy-4-methoxyphenyl) -2- (methylsulfonyl) ethylamine |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107540600B (en) | 2019-07-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107540601B (en) | The convenient preparation method of 5R- benzyloxy amino piperidine -2S- formic acid esters and its oxalates | |
| CN107540600B (en) | A kind of recoverying and utilizing method of AVM hereinafter Batan intermediate production waste liquid | |
| CN104557600A (en) | Preparation method of sacubitril | |
| CN105017082B (en) | A kind of preparation method of heart failure medicine Entresto key intermediates (R) tert-butyl group (base of 1 ([1,1` biphenyl] 4 bases) 3 hydroxy propane 2) carbamate | |
| EP3845523B1 (en) | Synthesis method for cariprazine | |
| CN109970625A (en) | A kind of preparation method of 5R- benzyloxy amino piperidine -2S- formic acid or derivatives thereof | |
| CN102633657A (en) | Preparation method of cis-3-amino-cyclopentanol hydrochloride | |
| CN106279175A (en) | A kind of preparation method of Ertapenem Sodium | |
| CN106496199A (en) | His Wei of Dacca and its preparation method of intermediate | |
| CN109053525A (en) | The preparation method of one kind (R) -2- (2- substitution -5- fluorobenzene) pyrrolidines | |
| CN104098462B (en) | The method for splitting of the diphenyl-propionic acid racemoid of 2 hydroxyl, 3 methoxyl group 3,3 | |
| CN111333561B (en) | Synthetic method of ralotinib intermediate (2R) -2- (2, 5-difluorophenyl) pyrrolidine | |
| CN101088985A (en) | Amfebutamone hydrochloride synthesizing process | |
| WO2013190481A1 (en) | Process for preparing asenapine and salts of intermediates thereof | |
| CN103524305B (en) | Preparation method of 1,3-propanediol derivatives and intermediates | |
| CN114163445B (en) | Larotinib intermediate and preparation method thereof | |
| CN105294828B (en) | The preparation method of Ao Beitawei | |
| CN108409557A (en) | Bu Waxitan new intermediates and its synthetic method and application | |
| CN107021969A (en) | The method that catalysis oxidation prepares biotin precursor ketone acid | |
| CN109265385B (en) | Synthesis process of chiral catalyst | |
| CN109053585B (en) | Synthetic method of triclabendazole | |
| CN106117204A (en) | The preparation method of Lei Dipawei intermediate (1R, 3S, 4S) 2 Boc 2 azabicyclo [2.2.1] pentane 3 carboxylic acid | |
| CN101462970B (en) | Process for synthesizing chiral methoxybenzylamine | |
| CN114380729B (en) | Preparation method of high-purity vildagliptin | |
| CN109574778A (en) | A kind of preparation method of Bu Waxitan and its intermediate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A method for recycling and utilizing waste liquid from the production of avibactam intermediates Effective date of registration: 20231205 Granted publication date: 20190709 Pledgee: Hengfeng bank Limited by Share Ltd. Dongying branch Pledgor: Xinfa pharmaceutical Co.,Ltd. Registration number: Y2023980069314 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right |