CN104892444B - 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
- CN104892444B CN104892444B CN201510332980.XA CN201510332980A CN104892444B CN 104892444 B CN104892444 B CN 104892444B CN 201510332980 A CN201510332980 A CN 201510332980A CN 104892444 B CN104892444 B CN 104892444B
- Authority
- CN
- China
- Prior art keywords
- phpg
- methyl esters
- resolving agent
- agent salt
- consumption
- 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
- 238000000034 method Methods 0.000 title claims abstract description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 87
- 150000003839 salts Chemical class 0.000 claims abstract description 53
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 51
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000013078 crystal Substances 0.000 claims abstract description 23
- 238000005886 esterification reaction Methods 0.000 claims abstract description 21
- 230000032050 esterification Effects 0.000 claims abstract description 20
- 239000007864 aqueous solution Substances 0.000 claims abstract description 19
- 239000000243 solution Substances 0.000 claims abstract description 17
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims abstract description 14
- 239000012452 mother liquor Substances 0.000 claims abstract description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 28
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 26
- 239000007788 liquid Substances 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 21
- 238000005406 washing Methods 0.000 claims description 17
- 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 14
- 229950007655 esilate Drugs 0.000 claims description 13
- 229960003742 phenol Drugs 0.000 claims description 13
- 238000010992 reflux Methods 0.000 claims description 13
- 239000006210 lotion Substances 0.000 claims description 11
- 239000012141 concentrate Substances 0.000 claims description 9
- -1 phenyl ethyl sulfonic acid sodium Chemical compound 0.000 claims description 8
- 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
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 150000004702 methyl esters Chemical class 0.000 claims description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 239000005864 Sulphur Substances 0.000 claims description 2
- 230000000384 rearing effect Effects 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 2
- 235000009508 confectionery Nutrition 0.000 claims 2
- JJVODHIRRAFJDE-UHFFFAOYSA-N 2-(hydroxyamino)-2-phenylacetic acid Chemical compound ONC(C(O)=O)C1=CC=CC=C1 JJVODHIRRAFJDE-UHFFFAOYSA-N 0.000 claims 1
- 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 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 229910021529 ammonia Inorganic materials 0.000 claims 1
- SZJUWKPNWWCOPG-UHFFFAOYSA-N methyl 2-anilinoacetate Chemical compound COC(=O)CNC1=CC=CC=C1 SZJUWKPNWWCOPG-UHFFFAOYSA-N 0.000 claims 1
- JKQOBWVOAYFWKG-UHFFFAOYSA-N molybdenum trioxide Chemical compound O=[Mo](=O)=O JKQOBWVOAYFWKG-UHFFFAOYSA-N 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 claims 1
- 229910001948 sodium oxide Inorganic materials 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000012065 filter cake Substances 0.000 description 15
- 239000011521 glass Substances 0.000 description 14
- 235000011121 sodium hydroxide Nutrition 0.000 description 11
- 238000010792 warming Methods 0.000 description 11
- 238000006386 neutralization reaction Methods 0.000 description 10
- 238000004519 manufacturing process Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 239000002994 raw material Substances 0.000 description 8
- 238000004821 distillation Methods 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 5
- 230000018044 dehydration Effects 0.000 description 5
- 238000006297 dehydration reaction Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 238000007605 air drying Methods 0.000 description 4
- 238000007599 discharging Methods 0.000 description 4
- 238000001914 filtration 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
- ZTJLYUVAFAMUKO-UHFFFAOYSA-N 2-phenylethanesulfonic acid Chemical compound OS(=O)(=O)CCC1=CC=CC=C1 ZTJLYUVAFAMUKO-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 3
- 239000000047 product Substances 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 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 2
- 229960003022 amoxicillin Drugs 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 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 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 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 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000006555 catalytic reaction 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
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 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
Abstract
Description
Claims (12)
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 CN104892444A (zh) | 2015-09-09 |
CN104892444B true 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) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
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 |
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 |
Also Published As
Publication number | Publication date |
---|---|
CN104892444A (zh) | 2015-09-09 |
WO2016202252A1 (zh) | 2016-12-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN104892444B (zh) | 一种合成d-对羟基苯甘氨酸甲酯的方法 | |
CN102321122B (zh) | 一种从三氯蔗糖-6-酯制备三氯蔗糖的方法 | |
CN101434566A (zh) | 对甲砜基甲苯的生产工艺 | |
CN104098461A (zh) | 一种β-羟基-β-甲基丁酸的纯化方法 | |
CN101896484B (zh) | 可可碱生产方法 | |
CN104356146B (zh) | 一种头孢替安盐酸盐的制备方法 | |
CN104910178A (zh) | 一种哌拉西林酸的制备方法 | |
CN102584928B (zh) | 一种反式甘草酸的制备方法 | |
CN104529935A (zh) | 高纯度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 | |
CN105985251A (zh) | 一种亚氨基二乙酸等氨基酸类清洁生产工艺 | |
CN108658871B (zh) | 周效磺胺中间体4,6-二氯-5-甲氧基嘧啶的制备方法 | |
CN108997209B (zh) | 一种瑞戈非尼的制备方法 | |
CN103265443A (zh) | 一种工业生产高纯度亚氨基二乙酸的方法 | |
CN102093435B (zh) | 一种从含阿拉伯糖的混合糖中提取阿拉伯糖的方法 | |
CN101514156A (zh) | 超重力场回收萘普生拆分溶剂、拆分剂及副产物的方法 | |
CN103755577B (zh) | 一种从盐酸氨溴索精制母液中回收氨溴索碱的方法 | |
CN102757367A (zh) | 一种混旋苯乙磺酸的拆分工艺 | |
CN110041233B (zh) | N-脂肪酰基-n-甲基牛磺酸钠的制备方法 | |
CN103626695B (zh) | 一种以混合溶剂为介质制备氟啶胺的新方法 | |
CN102336685B (zh) | 一种连续脱水制备氰乙酸的方法 | |
CN102234239A (zh) | 甘氨酸乙酯盐酸盐的优化工艺 | |
CN104529847A (zh) | 一种生产灭多威的方法 | |
CN103694285B (zh) | 一种异丙基-β-D-硫代半乳糖苷的制备方法 | |
CN104529812B (zh) | 一种盐酸丙胺卡因的制备方法 | |
CN101875659A (zh) | 替卡西林钠的制备工艺 |
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 | ||
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. |
|
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 | ||
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. |