CN104892444A - 一种合成d-对羟基苯甘氨酸甲酯的方法 - Google Patents
一种合成d-对羟基苯甘氨酸甲酯的方法 Download PDFInfo
- Publication number
- CN104892444A CN104892444A CN201510332980.XA CN201510332980A CN104892444A CN 104892444 A CN104892444 A CN 104892444A CN 201510332980 A CN201510332980 A CN 201510332980A CN 104892444 A CN104892444 A CN 104892444A
- Authority
- CN
- China
- Prior art keywords
- methyl ester
- resolving agent
- para hydroxybenzene
- glycine methyl
- phpg
- 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
- 238000000034 method Methods 0.000 title claims abstract description 50
- 230000002194 synthesizing effect Effects 0.000 title abstract description 5
- SZBDOFWNZVHVGR-MRVPVSSYSA-N methyl (2r)-2-amino-2-(4-hydroxyphenyl)acetate Chemical compound COC(=O)[C@H](N)C1=CC=C(O)C=C1 SZBDOFWNZVHVGR-MRVPVSSYSA-N 0.000 title abstract 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 96
- 150000003839 salts Chemical class 0.000 claims abstract description 57
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 52
- 239000013078 crystal Substances 0.000 claims abstract description 28
- 238000005886 esterification reaction Methods 0.000 claims abstract description 24
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000012452 mother liquor Substances 0.000 claims abstract description 15
- 239000007864 aqueous solution Substances 0.000 claims abstract description 12
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 156
- 229960003742 phenol Drugs 0.000 claims description 78
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 claims description 71
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 45
- 239000000243 solution Substances 0.000 claims description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 30
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 claims description 29
- 230000032050 esterification Effects 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 21
- -1 Phenyl-ethanesulfonic acid sodium Chemical compound 0.000 claims description 16
- IAVPGZZRAJUOGE-UHFFFAOYSA-N [n'-(2-hydroxy-2-phenylethyl)carbamimidoyl]azanium;carbonate Chemical compound [O-]C([O-])=O.NC([NH3+])=NCC(O)C1=CC=CC=C1.NC([NH3+])=NCC(O)C1=CC=CC=C1 IAVPGZZRAJUOGE-UHFFFAOYSA-N 0.000 claims description 16
- 238000005406 washing Methods 0.000 claims description 15
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 13
- 239000006210 lotion Substances 0.000 claims description 11
- 239000002994 raw material Substances 0.000 claims description 11
- 238000010992 reflux Methods 0.000 claims description 9
- 238000011084 recovery Methods 0.000 claims description 7
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 239000006227 byproduct Substances 0.000 claims description 3
- 239000012141 concentrate Substances 0.000 claims description 3
- 230000000384 rearing effect Effects 0.000 claims description 2
- 239000007788 liquid Substances 0.000 abstract description 27
- 230000015572 biosynthetic process Effects 0.000 abstract description 15
- 238000003786 synthesis reaction Methods 0.000 abstract description 15
- 229910000000 metal hydroxide Inorganic materials 0.000 abstract 2
- 150000004692 metal hydroxides Chemical class 0.000 abstract 2
- LJCWONGJFPCTTL-SSDOTTSWSA-N D-4-hydroxyphenylglycine Chemical compound [O-]C(=O)[C@H]([NH3+])C1=CC=C(O)C=C1 LJCWONGJFPCTTL-SSDOTTSWSA-N 0.000 abstract 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 239000012065 filter cake Substances 0.000 description 16
- 239000011521 glass Substances 0.000 description 14
- 238000010792 warming Methods 0.000 description 11
- 238000003756 stirring Methods 0.000 description 9
- 238000004821 distillation Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 238000006386 neutralization reaction Methods 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- 230000018044 dehydration Effects 0.000 description 5
- 238000006297 dehydration reaction Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- COFMBBYARPOGBA-UHFFFAOYSA-N 1-phenylethanesulfonic acid Chemical compound OS(=O)(=O)C(C)C1=CC=CC=C1 COFMBBYARPOGBA-UHFFFAOYSA-N 0.000 description 4
- 238000007605 air drying Methods 0.000 description 4
- 238000007599 discharging Methods 0.000 description 4
- 238000000703 high-speed centrifugation Methods 0.000 description 4
- 238000009413 insulation Methods 0.000 description 4
- 238000005498 polishing Methods 0.000 description 4
- 150000004684 trihydrates Chemical class 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 229940095064 tartrate Drugs 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- XUJHKPSBHDQIOD-UHFFFAOYSA-N (2-bromo-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl)methanesulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)C(Br)C1C2(C)C XUJHKPSBHDQIOD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 229960003022 amoxicillin Drugs 0.000 description 1
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
- C07C227/42—Crystallisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims (10)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510332980.XA CN104892444B (zh) | 2015-06-16 | 2015-06-16 | 一种合成d-对羟基苯甘氨酸甲酯的方法 |
PCT/CN2016/085804 WO2016202252A1 (zh) | 2015-06-16 | 2016-06-15 | 一种合成d-对羟基苯甘氨酸甲酯的方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510332980.XA CN104892444B (zh) | 2015-06-16 | 2015-06-16 | 一种合成d-对羟基苯甘氨酸甲酯的方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN104892444A true CN104892444A (zh) | 2015-09-09 |
CN104892444B CN104892444B (zh) | 2016-05-11 |
Family
ID=54025467
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201510332980.XA Active CN104892444B (zh) | 2015-06-16 | 2015-06-16 | 一种合成d-对羟基苯甘氨酸甲酯的方法 |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN104892444B (zh) |
WO (1) | WO2016202252A1 (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016202252A1 (zh) * | 2015-06-16 | 2016-12-22 | 山西新宝源制药有限公司 | 一种合成d-对羟基苯甘氨酸甲酯的方法 |
CN109400491A (zh) * | 2018-11-02 | 2019-03-01 | 威海海洋职业学院 | 一种左旋对羟基苯甘氨酸甲酯的结晶制备方法 |
CN111153821A (zh) * | 2019-12-25 | 2020-05-15 | 国药集团大同威奇达中抗制药有限公司 | D-对羟基苯甘氨酸甲酯的制备方法 |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113214103B (zh) * | 2021-04-23 | 2023-05-02 | 内蒙古常盛制药有限公司 | 一种酶法合成d-对羟基苯甘氨酸的后续处理方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103553949A (zh) * | 2013-10-11 | 2014-02-05 | 孟兰尊 | 一种α-氨基-对羟基苯乙酸甲酯或其硫酸盐的制备方法 |
CN104529801A (zh) * | 2014-12-31 | 2015-04-22 | 河南新天地药业股份有限公司 | 一种左旋对羟基苯甘氨酸的合成方法 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103113250A (zh) * | 2013-03-08 | 2013-05-22 | 华北制药集团先泰药业有限公司 | 一种d-对羟基苯甘氨酸甲酯的制备方法 |
CN104892444B (zh) * | 2015-06-16 | 2016-05-11 | 山西新宝源制药有限公司 | 一种合成d-对羟基苯甘氨酸甲酯的方法 |
-
2015
- 2015-06-16 CN CN201510332980.XA patent/CN104892444B/zh active Active
-
2016
- 2016-06-15 WO PCT/CN2016/085804 patent/WO2016202252A1/zh active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103553949A (zh) * | 2013-10-11 | 2014-02-05 | 孟兰尊 | 一种α-氨基-对羟基苯乙酸甲酯或其硫酸盐的制备方法 |
CN104529801A (zh) * | 2014-12-31 | 2015-04-22 | 河南新天地药业股份有限公司 | 一种左旋对羟基苯甘氨酸的合成方法 |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016202252A1 (zh) * | 2015-06-16 | 2016-12-22 | 山西新宝源制药有限公司 | 一种合成d-对羟基苯甘氨酸甲酯的方法 |
CN109400491A (zh) * | 2018-11-02 | 2019-03-01 | 威海海洋职业学院 | 一种左旋对羟基苯甘氨酸甲酯的结晶制备方法 |
CN109400491B (zh) * | 2018-11-02 | 2021-03-23 | 威海海洋职业学院 | 一种左旋对羟基苯甘氨酸甲酯的结晶制备方法 |
CN111153821A (zh) * | 2019-12-25 | 2020-05-15 | 国药集团大同威奇达中抗制药有限公司 | D-对羟基苯甘氨酸甲酯的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN104892444B (zh) | 2016-05-11 |
WO2016202252A1 (zh) | 2016-12-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN104892444A (zh) | 一种合成d-对羟基苯甘氨酸甲酯的方法 | |
CN109485633A (zh) | 一种硫酸乙烯酯的制备方法 | |
CN105330609B (zh) | 一种制备lcz696的方法 | |
CN105236452A (zh) | 一种硝酸钠与氯化钾反应生产高纯硝酸钾的工艺 | |
CN102757462A (zh) | 草甘膦结晶连续化生产方法 | |
CN104710351B (zh) | 一种维生素b6的连续制备方法 | |
CN104119243A (zh) | 一种亚氨基二乙酸的节能清洁生产方法 | |
CN106916138A (zh) | 一种甲烷二磺酸亚甲酯的合成方法 | |
CN104529935B (zh) | 2‑(3‑醛基‑4‑异丁氧基苯基)‑4‑甲基噻唑‑5‑甲酸乙酯的合成方法 | |
CN101734690A (zh) | 一种溶剂萃取法制取硝酸钾的方法 | |
CN103145645B (zh) | 甲基巯基噻二唑的制备工艺 | |
CN107406401B (zh) | 用于由固体盐制造呋喃-2,5-二甲酸(fdca)的方法 | |
CN103265443A (zh) | 一种工业生产高纯度亚氨基二乙酸的方法 | |
CN103242342B (zh) | 1,3-烷基四氢噻吩并[3,4-d]咪唑-2(3H)-4-二酮化合物的制备方法 | |
CN105622666A (zh) | 草甘膦的合成工艺 | |
CN102757367A (zh) | 一种混旋苯乙磺酸的拆分工艺 | |
CN110938020B (zh) | 一种月桂酰精氨酸乙酯盐酸盐的制备工艺 | |
CN109836344B (zh) | 一种有机溶剂生产甘氨酸的方法 | |
CN113697829A (zh) | 一种氟化锂的制备方法 | |
CN102336685B (zh) | 一种连续脱水制备氰乙酸的方法 | |
CN112159388A (zh) | 一种硫酸乙烯酯衍生物的制备方法 | |
CN111303045A (zh) | 2-乙氧基-4,6-二氟嘧啶的生产工艺 | |
CN106478402A (zh) | 由乙醇酸甲酯制备乙醇酸晶体的方法 | |
CN109776448B (zh) | 一种非布司他a晶型的制备方法 | |
CN110923276B (zh) | 一种生物酶催化合成天门冬氨酸钙的制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
C41 | Transfer of patent application or patent right or utility model | ||
GR01 | Patent grant | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20160420 Address after: 037002 Shanxi province Datong Xinrong District Garden Tun Xiang Industrial Park Applicant after: SHANXI XINBAOYUAN PHARMACEUTICAL Co.,Ltd. Address before: 037008 Shanxi province Datong Pharmaceutical Industrial Park on the north side of Central Avenue Applicant before: SHANXI XINGHUO WEIMIN PHARMACEUTICAL Co.,Ltd. |
|
CP02 | Change in the address of a patent holder |
Address after: 037010 Datong pharmaceutical industry park, Shanxi Patentee after: SHANXI XINBAOYUAN PHARMACEUTICAL Co.,Ltd. Address before: 037002 Shanxi province Datong Xinrong District Garden Tun Xiang Industrial Park Patentee before: Shanxi Xinbaoyuan Pharmaceutical Co.,Ltd. |
|
CP02 | Change in the address of a patent holder | ||
CP01 | Change in the name or title of a patent holder | ||
CP01 | Change in the name or title of a patent holder |
Address after: 037010 Datong Pharmaceutical Industrial Park, Shanxi Patentee after: Shanxi Shuangyan Pharmaceutical Co.,Ltd. Address before: 037010 Datong Pharmaceutical Industrial Park, Shanxi Patentee before: SHANXI XINBAOYUAN PHARMACEUTICAL Co.,Ltd. |
|
TR01 | Transfer of patent right |
Effective date of registration: 20230220 Address after: 037000 North side of Central Avenue, Second Pharmaceutical Industrial Park, Yunzhou District, Datong City, Shanxi Province Patentee after: Shanxi Shuangyan Biotechnology Co.,Ltd. Address before: 037010 Datong Pharmaceutical Industrial Park, Shanxi Patentee before: Shanxi Shuangyan Pharmaceutical Co.,Ltd. |
|
TR01 | Transfer of patent right |