CN106588698B - A kind of preparation method of the third ammonium aldehyde of N-Boc biphenyl - Google Patents
A kind of preparation method of the third ammonium aldehyde of N-Boc biphenyl Download PDFInfo
- Publication number
- CN106588698B CN106588698B CN201611015731.9A CN201611015731A CN106588698B CN 106588698 B CN106588698 B CN 106588698B CN 201611015731 A CN201611015731 A CN 201611015731A CN 106588698 B CN106588698 B CN 106588698B
- Authority
- CN
- China
- Prior art keywords
- preparation
- boc
- biphenyl
- iodosobenzoic acid
- oxidation reaction
- 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.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Abstract
The invention discloses a kind of preparation methods of the third ammonium aldehyde of N-Boc- biphenyl comprising following step: in organic solvent, N-Boc- biphenyl Propanolamine and 2- iodosobenzoic acid being carried out oxidation reaction, obtain the third ammonium aldehyde of N-Boc- biphenyl.This method is easy to operate, high income, purity is high, at low cost, pollution less, be suitble to industrialized production.
Description
Technical field
The present invention relates to a kind of preparation methods of the third ammonium aldehyde of N-Boc biphenyl, belong to field of medicine and chemical technology.
Background technique
The new drug Entresto for the treatment cardiovascular disease that Novartis Co., Ltd releases recently, for treating II-IV grade of heart of NYHA
Decline patient, in many ways cardioactive neuroendocrine system.Entresto is the anti-hypertension for losing patent protection
Drug Valsartan and a kind of combination drug of novel antihypertensive medicament Sacubitril, the treatment for heart failure.
Synthesis for newtype drug Sacubitril enkephalinase inhibitor, though document has the report of several different routes
Road, but it is directed to the conversion that N-Boc biphenyl Propanolamine is converted into the third ammonium aldehyde of N-Boc biphenyl mostly.This related oxidation process,
Only seeing nine divisions of China in remote antiquity medicine company and Novartis Co., Ltd reports the technique using TEMPO catalysis oxidation in WO2014032627 at present.The work
The advantages of skill, is that raw material is relatively inexpensive, but cumbersome, and solvent usage is big, and system is huge, and the yield of products therefrom is generally 70
~75%.
Therefore, this field need a kind of easy to operate, high income, purity is high, at low cost, pollution less, be suitble to industrial metaplasia
The preparation method of the third ammonium aldehyde of N-Boc- biphenyl of production.
Summary of the invention
Problem to be solved by this invention is that the preparation method of existing the third ammonium aldehyde of N-Boc- biphenyl is cumbersome, yield is low
The defects of, thus, the present invention provides a kind of preparation methods of the third ammonium aldehyde of N-Boc- biphenyl.This method is easy to operate, high income,
It is with high purity, at low cost, pollution less, be suitble to industrialized production.
The present invention provides a kind of preparation methods of the third ammonium aldehyde of N-Boc- biphenyl comprising following step: in organic solvent
In, N-Boc- biphenyl Propanolamine and 2- iodosobenzoic acid (IBX) are subjected to oxidation reaction, obtain the third ammonium aldehyde of N-Boc- biphenyl i.e.
It can;
Wherein, " * " in the N-Boc- biphenyl Propanolamine and third ammonium aldehyde of N-Boc- biphenyl indicates mark
Carbon atom is asymmetric carbon atom, and its configuration identical (therefore, the N-Boc- biphenyl Propanolamine and the N-Boc- biphenyl
Third ammonium aldehyde is the mixture of R configuration, S configuration or R configuration and S configuration simultaneously;Namely configuration reversal does not occur for the reaction).
In the oxidation reaction, the organic solvent that the organic solvent can be conventional for such reaction of this field, this
Invent one of particularly preferred nitrile solvents, aromatic hydrocarbon solvent and ether solvent or a variety of, further preferred ether solvent.
The ether solvent can be the ether solvent of such reaction routine of this field, 1,2- dimethoxy-ethane specifically preferred according to the invention
(DME).The aromatic hydrocarbon solvent can be the aromatic hydrocarbon solvent of such reaction routine of this field, first specifically preferred according to the invention
Benzene.The nitrile solvents can be the nitrile solvents of such reaction routine of this field, acetonitrile specifically preferred according to the invention.
In the oxidation reaction, the volume mass ratio of the organic solvent and the N-Boc- biphenyl Propanolamine
It can be the volume mass ratio of such reaction routine of this field, preferably 3~12mL/g is more preferably 4~8mL/g, most preferably
For 5~6mL/g.
In the oxidation reaction, mole of the 2- iodosobenzoic acid and the N-Boc- biphenyl Propanolamine
The conventional molar ratio than that can be such reaction of this field, preferably 1.0~2.0, more preferably for 1.1~1.6 (such as 1.3~
1.4)。
In the oxidation reaction, the temperature that the temperature of the oxidation reaction can be conventional for such reaction of this field,
Preferably 30~120 DEG C (in another example 110 DEG C), be more preferably 50~90 DEG C, is most preferably 75~85 DEG C.
In the oxidation reaction, the oxidation reaction can be used such reaction conventional detection mode of this field and carry out
Monitoring, such as thin-layer chromatography (TLC).When carrying out reaction end monitoring with TLC, generally no longer reacted with N-Boc- biphenyl Propanolamine
Terminal as reaction.The time of the oxidation reaction can for 0.5~3 hour (such as 0.5~2 hour, in another example 1 is small
When).
The oxidation reaction can further include the conventional post-processing of such reaction of this field.Preferably, the oxidation is anti-
It should further include following post-processing steps: cooling (such as being down to room temperature), filtering, with above-mentioned organic solvent washing filter cake (i.e. 2-
Iodosobenzoic acid crude product), filtrate concentration (partially completely removes reaction dissolvent, above-mentioned organic solvent), recrystallization
(recrystallization solvent can be ethyl acetate/normal heptane) obtains third ammonium aldehyde of N-Boc- biphenyl.
Preferably, the post-processing step of the oxidation reaction further includes following step, will handle in the above-mentioned latter
Reoxidized obtained filter cake (i.e. 2- iodosobenzoic acid crude product) is 2- iodosobenzoic acid, is recycled to realize,
And work well: in water, the filter cake (i.e. 2- iodosobenzoic acid crude product) and oxidant being subjected to oxidation reaction, obtained
To 2- iodosobenzoic acid;
In the preparation method of the 2- iodosobenzoic acid, the oxidant can such reaction be conventional for this field
Oxidant (such as potassium permanganate or potassium hydrogen persulfate), preferably potassium hydrogen persulfate.
In the preparation method of the 2- iodosobenzoic acid, the oxidant and filter cake (the i.e. 2- idous
Acyl group benzoic acid crude product) molar ratio can be conventional for such reaction of this field molar ratio, preferably 2.0~3.6, more preferably
It is 2.7~3.0.When calculating the mole of the filter cake, it is assumed that the filter cake is 2- iodosobenzoic acid sterling.
In the preparation method of the 2- iodosobenzoic acid, the temperature of the oxidation reaction can for this field such
Conventional temperature is reacted, it is most preferably 65~75 DEG C that preferably 30~100 DEG C, which be more preferably 50~90 DEG C,.
In the preparation method of the 2- iodosobenzoic acid, such reaction of this field is can be used in the oxidation reaction
Conventional detection mode is monitored, such as thin-layer chromatography (TLC).When carrying out reaction end monitoring with TLC, generally with 2- iodoso
Terminal of the yl benzoic acid residual less than 2% as reaction.
Without prejudice to the field on the basis of common sense, above-mentioned each optimum condition, can any combination to get the present invention it is each preferably
Example.
The reagents and materials used in the present invention are commercially available.
The positive effect of the present invention is that: this method is easy to operate, high income, purity is high, at low cost, pollution less,
It is suitble to industrialized production
Specific embodiment
The present invention is further illustrated below by the mode of embodiment, but does not therefore limit the present invention to the reality
It applies among a range.In the following examples, the experimental methods for specific conditions are not specified, according to conventional methods and conditions, or according to quotient
The selection of product specification.
The measurement method of embodiment moderate purity is as follows: HPLC, chromatographic column: Gemini C18,250 × 4.6mmID, 5 μm, stream
Speed: 1.0mL/min, column temperature: 30 DEG C.Mobile phase A (20mM KH2PO4Aqueous solution is added 6mol/L KOH and adjusts pH=10), stream
Dynamic phase B (MeOH).Gradient: 0min (70%A);20min (30%A);40min (30%A).Acquisition time: 40 minutes.
Retention time:
(R)-N-Boc-3- (1,1 '-biphenyl -4- base) -2- aminopropanol: 30.3min
(R)-N-Boc-3- (1,1 '-biphenyl -4- base) -2- amido propionic aldehyde: 32.0min
2- iodosobenzoic acid: 3.4min
2- iodosobenzoic acid: 4.2min
Embodiment 1 (R)-N-Boc-3- (1,1 '-biphenyl -4- base) -2- amido propionic aldehyde
In the round-bottomed flask of 1L, 105g (R)-N-Boc-3- (1,1 '-biphenyl -4- base) -2- aminopropanol is dissolved in
In 600mL DME, under stirring, 117g IBX is added.After adding, reaction system is heated to 75-85 DEG C, is reacted 1 hour
Left and right monitoring to raw material disappears, and reaction system is cooled down to room temperature.Filtering, filter cake are eluted with 50mL DME, after filter cake is collected
As 2- iodosobenzoic acid, it is used for subsequent recycling and is crystallized after filtrate decompression concentration with ethyl acetate/normal heptane, drying
After obtain white solid 101g, as target product.Yield 96.6%, purity > 99%.
1H-NMR(400MHz,CDCl3): δ=9.69 (s, 1H), 7.59 (t, 4H), 7.46 (t, 2H), 7.38 (t, 1H),
7.28(d,2H),5.13(d,1H),4.48(q,1H),3.18(d,2H),1.47(s,9H)。
The 2- iodosobenzoic acid of the recycling of embodiment 2 prepares IBX
In the round-bottomed flask of 1L, the 2- iodosobenzoic acid recycled in 40g above-described embodiment 1 is added, configuration is added
(145g potassium hydrogen persulfate is dissolved in 500mL water good hydrogen persulfate aqueous solutions of potassium, and the active constituent content of potassium hydrogen persulfate is
42.8%).After adding, reaction system is heated to 65-75 DEG C, is reacted 3 hours or so, monitoring to 2- idous acyl group benzene first
Acid residual is less than 2%.Reaction system is cooled down to 0-5 DEG C, is stirred 2 hours.Filtering, filter cake are washed with water repeatedly, after drying
Obtain white solid 38.6g, as IBX.The rate of recovery 85.4%, purity > 98%.
(IBX is the 2- iodoso with recycling to embodiment 3 (R)-N-Boc-3- (1,1 '-biphenyl -4- base) -2- amido propionic aldehyde
Yl benzoic acid preparation gained)
In the round-bottomed flask of 250mL, 26g (R)-N-Boc-3- (1,1 '-biphenyl -4- base) -2- aminopropanol is dissolved in
In 160mL DME, under stirring, it is added in 29g embodiment 2 and recycles the IBX of preparation.After adding, reaction system is heated to
It 75-85 DEG C, reacts monitoring in 1 hour or so to raw material and disappears, reaction system is cooled down into room temperature.Filtering, filter cake 15mL
DME elution, filter cake are used as 2- iodosobenzoic acid after collecting, can be repeated for subsequent recycling.After filtrate decompression concentration, use
Ethyl acetate/normal heptane crystallization, obtains white solid 25g, as target product after drying.Yield 96.4%, purity > 99%.
Embodiment 4 (S)-N-Boc-3- (1,1 '-biphenyl -4- base) -2- amido propionic aldehyde
In the round-bottomed flask of 1L, 105g (S)-N-Boc-3- (1,1 '-biphenyl -4- base) -2- aminopropanol is dissolved in
In 300mL acetonitrile, under stirring, 90g IBX is added.After adding, reaction system is heated to 50-55 DEG C, reacts 2 hours left sides
Right monitoring to raw material disappears, and reaction system is cooled down to room temperature.Filtering, filter cake are eluted with 50mL acetonitrile, and filter cake is made after collecting
For 2- iodosobenzoic acid, it is used for subsequent recycling and is crystallized with ethyl acetate/normal heptane, after drying after filtrate decompression concentration
Obtain white solid 92g, as target product.Yield 88%, purity > 98%.
Embodiment 5 (R)-N-Boc-3- (1,1 '-biphenyl -4- base) -2- amido propionic aldehyde
In the round-bottomed flask of 1L, 105g (R)-N-Boc-3- (1,1 '-biphenyl -4- base) -2- aminopropanol is dissolved in
In 800mL toluene, under stirring, 144g IBX is added.After adding, reaction system is heated to 110 DEG C of reflux, reaction 1 is small
When or so monitoring to raw material disappear, reaction system is cooled down into room temperature.Filtering, filter cake are eluted with 50mL toluene, and filter cake is collected
It is used as 2- iodosobenzoic acid afterwards, is used for subsequent recycling and is crystallized after filtrate decompression concentration with ethyl acetate/normal heptane, dried
White solid 89g, as target product are obtained after dry.Yield 85%, purity > 99%.
Embodiment 6 (R)-N-Boc-3- (1,1 '-biphenyl -4- base) -2- amido propionic aldehyde
In the round-bottomed flask of 1L, 105g (R)-N-Boc-3- (1,1 '-biphenyl -4- base) -2- aminopropanol is dissolved in
In 400mL DME, under stirring, 100g IBX is added.After adding, reaction system is heated to 30~35 DEG C, is reacted 3 hours
Left and right monitoring to raw material disappears, and reaction system is cooled down to room temperature.Filtering, filter cake are eluted with 50mL DME, after filter cake is collected
As 2- iodosobenzoic acid, it is used for subsequent recycling and is crystallized after filtrate decompression concentration with ethyl acetate/normal heptane, drying
After obtain white solid 97g, as target product.Yield 93%, purity > 99%.
Embodiment 7 (R)-N-Boc-3- (1,1 '-biphenyl -4- base) -2- amido propionic aldehyde
In the round-bottomed flask of 1L, 105g (R)-N-Boc-3- (1,1 '-biphenyl -4- base) -2- aminopropanol is dissolved in
In 1200mL toluene, under stirring, 180g IBX is added.After adding, reaction system is heated to 90-95 DEG C, is reacted 1 hour
Left and right monitoring to raw material disappears, and reaction system is cooled down to room temperature.Filtering, filter cake are eluted with 50mL toluene, after filter cake is collected
As 2- iodosobenzoic acid, it is used for subsequent recycling and is crystallized after filtrate decompression concentration with ethyl acetate/normal heptane, drying
After obtain white solid 90g, as target product.Yield 86%, purity > 98%.
Claims (8)
1. a kind of preparation method of the third ammonium aldehyde of N-Boc- biphenyl comprising following step: in organic solvent, by N-Boc- biphenyl
Propanolamine and 2- iodosobenzoic acid carry out oxidation reaction, obtain the third ammonium aldehyde of N-Boc- biphenyl;The organic solvent is
Toluene;The volume mass ratio of the organic solvent and the N-Boc- biphenyl Propanolamine is 8mL/g~12mL/g;Described
The molar ratio of 2- iodosobenzoic acid and the N-Boc- biphenyl Propanolamine is 1.6~2.0;The temperature of the oxidation reaction
It is 90 DEG C~110 DEG C;
Wherein, " * " in the N-Boc- biphenyl Propanolamine and third ammonium aldehyde of N-Boc- biphenyl indicates that the carbon of mark is former
Son is asymmetric carbon atom, and its configuration is identical.
2. preparation method as described in claim 1, which is characterized in that the N-Boc- biphenyl Propanolamine and the N-
The third ammonium aldehyde of Boc- biphenyl is the mixture of R configuration, S configuration or R configuration and S configuration simultaneously;
And/or the oxidation reaction no longer reacts the terminal as reaction using N-Boc- biphenyl Propanolamine.
3. preparation method as described in claim 1, which is characterized in that the oxidation reaction further includes following post-processing steps
Rapid: cooling, filtering, with the organic solvent washing filter cake, filtrate concentration, recrystallization obtains the N-Boc- biphenyl third
Ammonium aldehyde.
4. preparation method as claimed in claim 3, which is characterized in that the cooling is to be down to room temperature;
And/or solvent used in the recrystallization is ethyl acetate and normal heptane.
5. preparation method as claimed in claim 3, which is characterized in that the post-processing step of the oxidation reaction further includes
Following step: in water, the filter cake and oxidant is subjected to oxidation reaction, obtain 2- iodosobenzoic acid.
6. preparation method as claimed in claim 5, which is characterized in that in the preparation method of the 2- iodosobenzoic acid
In, the oxidant is potassium permanganate or potassium hydrogen persulfate;
And/or in the preparation method of the 2- iodosobenzoic acid, the molar ratio of the oxidant and the filter cake
It is 2.0~3.6;
And/or in the preparation method of the 2- iodosobenzoic acid, the temperature of the oxidation reaction is 30~100 DEG C;
And/or in the preparation method of the 2- iodosobenzoic acid, the oxidation reaction is with 2- iodosobenzoic acid
Remain the terminal less than 2% as reaction.
7. preparation method as claimed in claim 6, which is characterized in that in the preparation method of the 2- iodosobenzoic acid
In, the oxidant is potassium hydrogen persulfate;
And/or in the preparation method of the 2- iodosobenzoic acid, the molar ratio of the oxidant and the filter cake
It is 2.7~3.0;
And/or in the preparation method of the 2- iodosobenzoic acid, the temperature of the oxidation reaction is 50~90 DEG C.
8. preparation method as claimed in claim 7, which is characterized in that in the preparation method of the 2- iodosobenzoic acid
In, the temperature of the oxidation reaction is 65~75 DEG C.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201611015731.9A CN106588698B (en) | 2016-11-18 | 2016-11-18 | A kind of preparation method of the third ammonium aldehyde of N-Boc biphenyl |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201611015731.9A CN106588698B (en) | 2016-11-18 | 2016-11-18 | A kind of preparation method of the third ammonium aldehyde of N-Boc biphenyl |
Publications (2)
Publication Number | Publication Date |
---|---|
CN106588698A CN106588698A (en) | 2017-04-26 |
CN106588698B true CN106588698B (en) | 2019-01-22 |
Family
ID=58592280
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201611015731.9A Active CN106588698B (en) | 2016-11-18 | 2016-11-18 | A kind of preparation method of the third ammonium aldehyde of N-Boc biphenyl |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106588698B (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109293628A (en) * | 2018-09-29 | 2019-02-01 | 浙江国邦药业有限公司 | A method of preparing 2- iodosobenzoic acid |
CN110128298B (en) * | 2019-06-13 | 2021-08-03 | 南京一心和医药科技有限公司 | Synthetic method of Sacubitril intermediate |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5550119A (en) * | 1995-03-02 | 1996-08-27 | Ciba-Geigy Corporation | Phosphono substituted tetrazole derivatives as ECE inhibitors |
EP2148886B1 (en) * | 2007-05-10 | 2014-02-19 | R & D Biopharmaceuticals Gmbh | Tubulysine derivatives |
CN101070315B (en) * | 2007-05-11 | 2010-09-29 | 江苏工业学院 | Method for preparing omeprazole |
CN101508631B (en) * | 2009-03-31 | 2012-12-05 | 贵州大学 | Method for oxidizing ethanol into corresponding aldehyde in catalyst action |
CN102964267B (en) * | 2011-09-01 | 2015-06-10 | 中山大学 | Cyclohexene compound having influenza virus neuraminidase inhibition activity, preparation method and application |
AR092278A1 (en) * | 2012-08-31 | 2015-04-08 | Novartis Ag | PROCESS FOR OBTAINING N-ACILIC DERIVATIVES OF BIFENYL-ALANINE AND RELATED INTERMEDIARIES |
CN102924499B (en) * | 2012-10-22 | 2015-11-18 | 四川大学 | The synthesis of L-3,4,5-trioxy--phenylalanine/aldehyde cpd |
CN103242146A (en) * | 2013-05-23 | 2013-08-14 | 天宁香料(江苏)有限公司 | Preparation method of cis-3-hexenal |
CN105168205A (en) * | 2015-08-18 | 2015-12-23 | 泰力特医药(湖北)有限公司 | Preparation method for dual inhibitor LCZ696 of angiotensin II receptor and neprilysin |
CN106045902A (en) * | 2016-06-30 | 2016-10-26 | 苏州健雄职业技术学院 | Preparation method of 3-bromo-6-methyl-2-pyridylaldehyde |
-
2016
- 2016-11-18 CN CN201611015731.9A patent/CN106588698B/en active Active
Also Published As
Publication number | Publication date |
---|---|
CN106588698A (en) | 2017-04-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Su et al. | Nickel-catalyzed monofluoromethylation of aryl boronic acids | |
Romanelli et al. | Solvent-free catalytic preparation of 1, 1-diacetates from aldehydes using a Wells–Dawson acid (H6P2W18O62· 24H2O) | |
CN106588698B (en) | A kind of preparation method of the third ammonium aldehyde of N-Boc biphenyl | |
Bartoli et al. | The CeCl3· 7H2O–NaI system as promoter in the synthesis of functionalized trisubstituted alkenes via Knoevenagel condensation | |
CN107840819B (en) | Synthesis method of polysubstituted isoindolinone derivative | |
Ballini et al. | Nitroalkanes and ethyl glyoxalate as common precursors for the preparation of both β-keto esters and α, β-unsaturated esters | |
Peng et al. | Efficient enantioselective fluorination of β-keto esters/amides catalysed by diphenylamine-linked bis (thiazoline)–Cu (OTf) 2 complexes | |
CN109232212B (en) | Method for synthesizing methyl heptenone from isopentenol | |
CN112442008B (en) | Method for preparing 1, 4-dithiine and thiophene compounds by regulating elemental sulfur and active internal alkyne at temperature and conversion reaction of compound | |
CN103724151B (en) | Method for synthesizing 9-aryl fluorene compound | |
CN104693025B (en) | A kind of method preparing 1,3-propanedicarboxylic acid list L-menthyl ester | |
CN103102264B (en) | Preparation method of salicylic acid compound | |
CN112299981B (en) | Preparation method of alpha, alpha-difluoroketone derivative | |
CN101967102B (en) | Synthesizing method of N,N-diethyl-3,7-dimethyl-(E)-2,6-octadiene-1-amine | |
CN114293210A (en) | Method for continuously electrosynthesis of benzopyran-4-ketone by using micro-reaction device | |
Zhang et al. | A novel general method for preparation of α-fluoro-α-arylcarboxylic acid. Direct fluorination of silyl ketene acetals with Selectfluor® | |
Xie et al. | Palladium-catalyzed borylation of m-dibromobenzene derivative and its applications in one-pot tandem Suzuki–Miyaura arenes synthesis | |
EP1366010A2 (en) | Method for producing vinyl, aryl and heteroaryl acetic acids and derivatives thereof | |
CN110028409B (en) | Polysubstituted naphthalene derivative and preparation method thereof | |
CN109265385B (en) | Synthesis process of chiral catalyst | |
CN111018779B (en) | 2- (3-isoquinolyl) -ethyl propionate derivative and synthetic method thereof | |
CN112441961B (en) | Synthetic method of 3-pyrroline-2-ketone compound | |
CN110407677B (en) | Preparation method and application of diphenylethanedione compound | |
CN106674011B (en) | A method of indenone derivative is synthesized by dimethyl sulfoxide | |
EP2597079A1 (en) | Method for producing optically active 1-bromo-1-[3,5-bis(trifluoromethyl)phenyl]ethane |
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 |