CN102603594A - Preparation method of (S)-oxiracetam - Google Patents
Preparation method of (S)-oxiracetam Download PDFInfo
- Publication number
- CN102603594A CN102603594A CN2011100235145A CN201110023514A CN102603594A CN 102603594 A CN102603594 A CN 102603594A CN 2011100235145 A CN2011100235145 A CN 2011100235145A CN 201110023514 A CN201110023514 A CN 201110023514A CN 102603594 A CN102603594 A CN 102603594A
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- CN
- China
- Prior art keywords
- ethyl ester
- water
- glycine ethyl
- preparation
- ester hydrochloride
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- IHLAQQPQKRMGSS-BYPYZUCNSA-N 2-[(4s)-4-hydroxy-2-oxopyrrolidin-1-yl]acetamide Chemical compound NC(=O)CN1C[C@@H](O)CC1=O IHLAQQPQKRMGSS-BYPYZUCNSA-N 0.000 title claims abstract description 23
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 58
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 52
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 48
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 45
- TXTWXQXDMWILOF-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl)azanium;chloride Chemical compound [Cl-].CCOC(=O)C[NH3+] TXTWXQXDMWILOF-UHFFFAOYSA-N 0.000 claims abstract description 35
- NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- 238000001953 recrystallisation Methods 0.000 claims abstract description 15
- 238000000746 purification Methods 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 9
- 238000005406 washing Methods 0.000 claims abstract description 9
- 239000012043 crude product Substances 0.000 claims abstract description 6
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 235000011114 ammonium hydroxide Nutrition 0.000 claims abstract description 4
- 239000000047 product Substances 0.000 claims description 48
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 24
- 229910021529 ammonia Inorganic materials 0.000 claims description 22
- 239000012141 concentrate Substances 0.000 claims description 20
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 20
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 20
- 238000003756 stirring Methods 0.000 claims description 17
- 238000002425 crystallisation Methods 0.000 claims description 15
- 230000002378 acidificating effect Effects 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 14
- 125000002091 cationic group Chemical group 0.000 claims description 13
- 235000019441 ethanol Nutrition 0.000 claims description 13
- 239000011347 resin Substances 0.000 claims description 13
- 229920005989 resin Polymers 0.000 claims description 13
- 230000008025 crystallization Effects 0.000 claims description 12
- 239000013078 crystal Substances 0.000 claims description 11
- 239000000706 filtrate Substances 0.000 claims description 11
- 239000003957 anion exchange resin Substances 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 238000004440 column chromatography Methods 0.000 claims description 6
- 238000004090 dissolution Methods 0.000 claims description 6
- 239000000284 extract Substances 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 6
- 238000000926 separation method Methods 0.000 claims description 6
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 2
- 150000004703 alkoxides Chemical class 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 238000004128 high performance liquid chromatography Methods 0.000 abstract description 7
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 abstract 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 229960001227 oxiracetam Drugs 0.000 description 17
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- IHLAQQPQKRMGSS-UHFFFAOYSA-N oxiracetam Chemical compound NC(=O)CN1CC(O)CC1=O IHLAQQPQKRMGSS-UHFFFAOYSA-N 0.000 description 10
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 9
- 239000003456 ion exchange resin Substances 0.000 description 8
- 229920003303 ion-exchange polymer Polymers 0.000 description 8
- 235000017550 sodium carbonate Nutrition 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 230000009286 beneficial effect Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 238000007670 refining Methods 0.000 description 3
- IHLAQQPQKRMGSS-SCSAIBSYSA-N 2-[(4r)-4-hydroxy-2-oxopyrrolidin-1-yl]acetamide Chemical compound NC(=O)CN1C[C@H](O)CC1=O IHLAQQPQKRMGSS-SCSAIBSYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 230000009435 amidation Effects 0.000 description 2
- 238000007112 amidation reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- FUDDLSHBRSNCBV-VKHMYHEASA-N (4s)-4-hydroxyoxolan-2-one Chemical compound O[C@@H]1COC(=O)C1 FUDDLSHBRSNCBV-VKHMYHEASA-N 0.000 description 1
- GGRLKHMFMUXIOG-UHFFFAOYSA-M 2-acetyloxyethyl(trimethyl)azanium;hydroxide Chemical compound [OH-].CC(=O)OCC[N+](C)(C)C GGRLKHMFMUXIOG-UHFFFAOYSA-M 0.000 description 1
- QVPLPSZGHFSYEQ-UHFFFAOYSA-N 2-amino-2-hydroxybutanoic acid Chemical compound CCC(N)(O)C(O)=O QVPLPSZGHFSYEQ-UHFFFAOYSA-N 0.000 description 1
- FWIBCWKHNZBDLS-UHFFFAOYSA-N 3-hydroxyoxolan-2-one Chemical compound OC1CCOC1=O FWIBCWKHNZBDLS-UHFFFAOYSA-N 0.000 description 1
- FUDDLSHBRSNCBV-UHFFFAOYSA-N 4-hydroxyoxolan-2-one Chemical compound OC1COC(=O)C1 FUDDLSHBRSNCBV-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229960002298 aminohydroxybutyric acid Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 150000004648 butanoic acid derivatives Chemical class 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- YQGDEPYYFWUPGO-UHFFFAOYSA-N gamma-amino-beta-hydroxybutyric acid Chemical compound [NH3+]CC(O)CC([O-])=O YQGDEPYYFWUPGO-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 230000001777 nootropic effect Effects 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 150000003440 styrenes Chemical class 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- DWAWYEUJUWLESO-UHFFFAOYSA-N trichloromethylsilane Chemical compound [SiH3]C(Cl)(Cl)Cl DWAWYEUJUWLESO-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201110023514.5A CN102603594B (en) | 2011-01-21 | 2011-01-21 | Preparation method of (S)-oxiracetam |
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CN201110023514.5A CN102603594B (en) | 2011-01-21 | 2011-01-21 | Preparation method of (S)-oxiracetam |
Publications (2)
Publication Number | Publication Date |
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CN102603594A true CN102603594A (en) | 2012-07-25 |
CN102603594B CN102603594B (en) | 2014-04-16 |
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CN201110023514.5A Active CN102603594B (en) | 2011-01-21 | 2011-01-21 | Preparation method of (S)-oxiracetam |
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CN (1) | CN102603594B (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103554000A (en) * | 2013-11-06 | 2014-02-05 | 重庆润泽医药有限公司 | (S)-oxiracetam crystal form III, and preparation method and application thereof |
CN106366031A (en) * | 2016-08-30 | 2017-02-01 | 山东默得森生物制药有限公司 | Preparation method of (S)-4-hydroxy-2-oxo-1-pyrrolidinyl acetamide |
CN107021912A (en) * | 2016-01-29 | 2017-08-08 | 重庆润泽医药有限公司 | The method that grinding prepares levo-oxiracetam crystal formation I |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1956953A (en) * | 2004-05-25 | 2007-05-02 | 安国药品株式会社 | Process for the preparation of optically pure 4-hydroxy-2-oxo-1-pyrrolidine acetamide |
CN101367757A (en) * | 2008-10-13 | 2009-02-18 | 重庆润泽医疗器械有限公司 | Preparation method for (S)-4-hydroxyl-2-oxo-1-pyrrolidine ethanamide |
US20100125096A1 (en) * | 2008-11-14 | 2010-05-20 | Neurotune Ag | Acetam Derivatives for Pain Relief |
-
2011
- 2011-01-21 CN CN201110023514.5A patent/CN102603594B/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1956953A (en) * | 2004-05-25 | 2007-05-02 | 安国药品株式会社 | Process for the preparation of optically pure 4-hydroxy-2-oxo-1-pyrrolidine acetamide |
CN101367757A (en) * | 2008-10-13 | 2009-02-18 | 重庆润泽医疗器械有限公司 | Preparation method for (S)-4-hydroxyl-2-oxo-1-pyrrolidine ethanamide |
US20100125096A1 (en) * | 2008-11-14 | 2010-05-20 | Neurotune Ag | Acetam Derivatives for Pain Relief |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103554000A (en) * | 2013-11-06 | 2014-02-05 | 重庆润泽医药有限公司 | (S)-oxiracetam crystal form III, and preparation method and application thereof |
CN103554000B (en) * | 2013-11-06 | 2015-03-11 | 重庆润泽医药有限公司 | (S)-oxiracetam crystal form III, and preparation method and application thereof |
US9670156B2 (en) | 2013-11-06 | 2017-06-06 | Chongqing Ruzer Pharmaceutical Company Limited | Crystal form III of (S)-oxiracetam, preparation method and use thereof |
CN107021912A (en) * | 2016-01-29 | 2017-08-08 | 重庆润泽医药有限公司 | The method that grinding prepares levo-oxiracetam crystal formation I |
CN106366031A (en) * | 2016-08-30 | 2017-02-01 | 山东默得森生物制药有限公司 | Preparation method of (S)-4-hydroxy-2-oxo-1-pyrrolidinyl acetamide |
Also Published As
Publication number | Publication date |
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CN102603594B (en) | 2014-04-16 |
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Address after: 400042 Chongqing city Yubei District Qinye Road No. 9 Applicant after: Chongqing Runze Pharmaceutical Co., Ltd. Address before: 401120 Chongqing city Yubei District Shuangfeng Bridge Street Airport Road No. 296 Building 1 yuan and 7 2- store Applicant before: Chongqing Runze Medical Instruments Ltd. |
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Owner name: CHONGQING DONGZE PHARMACEUTICAL TECHNOLOGY DEVELOP Free format text: FORMER OWNER: CHONGQING RUNZE PHARMACEUTICAL CO., LTD. Effective date: 20140306 |
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Effective date of registration: 20140306 Address after: 400030 Chongqing city Shapingba District Yubei Road No. 50 of No. 13-15-6A Applicant after: DONGZE PHARMACEUTICAL SCIENCE AND TECHNOLOGY CO., LTD. Address before: 400042 Chongqing city Yubei District Qinye Road No. 9 Applicant before: Chongqing Runze Pharmaceutical Co., Ltd. |
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CB03 | Change of inventor or designer information |
Inventor after: Ye Lei Inventor before: Ye Lei Inventor before: Chen Yuying Inventor before: Li Kun Inventor before: Rong Zuyuan Inventor before: Yu Yuanyuan Inventor before: Ping Yuan |
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Free format text: CORRECT: INVENTOR; FROM: YE LEI CHEN YUYING LI KUN RONG ZUYUAN YU YUANYUAN PING YUAN TO: YE LEI |
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Effective date of registration: 20170825 Address after: 400042 Chongqing city Yubei District Qinye Road No. 9 Patentee after: Chongqing Runze Pharmaceutical Co., Ltd. Address before: 400030 Chongqing city Shapingba District Yubei Road No. 50 of No. 13-15-6A Patentee before: DONGZE PHARMACEUTICAL SCIENCE AND TECHNOLOGY CO., LTD. |
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