CN102432516A - 奥拉西坦的精制方法 - Google Patents
奥拉西坦的精制方法 Download PDFInfo
- Publication number
- CN102432516A CN102432516A CN2011104185535A CN201110418553A CN102432516A CN 102432516 A CN102432516 A CN 102432516A CN 2011104185535 A CN2011104185535 A CN 2011104185535A CN 201110418553 A CN201110418553 A CN 201110418553A CN 102432516 A CN102432516 A CN 102432516A
- Authority
- CN
- China
- Prior art keywords
- oxiracetam
- bullion
- purification
- ethyl alcohol
- glacial acetic
- 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
- IHLAQQPQKRMGSS-UHFFFAOYSA-N oxiracetam Chemical compound NC(=O)CN1CC(O)CC1=O IHLAQQPQKRMGSS-UHFFFAOYSA-N 0.000 title claims abstract description 106
- 229960001227 oxiracetam Drugs 0.000 title claims abstract description 106
- 238000000034 method Methods 0.000 title claims abstract description 27
- 238000007670 refining Methods 0.000 title abstract description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 64
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 41
- 229960000583 acetic acid Drugs 0.000 claims abstract description 31
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract description 30
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 29
- 238000003756 stirring Methods 0.000 claims abstract description 22
- 239000012046 mixed solvent Substances 0.000 claims abstract description 15
- 238000010992 reflux Methods 0.000 claims abstract description 8
- 238000001035 drying Methods 0.000 claims abstract description 3
- 238000000746 purification Methods 0.000 claims description 17
- 239000000243 solution Substances 0.000 claims description 10
- 239000012266 salt solution Substances 0.000 claims description 5
- 238000010792 warming Methods 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 4
- 238000005119 centrifugation Methods 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 239000012535 impurity Substances 0.000 abstract description 10
- 238000010438 heat treatment Methods 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 2
- 238000001914 filtration Methods 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 239000000126 substance Substances 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 230000008025 crystallization Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000001476 alcoholic effect Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000000413 hydrolysate Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 238000005352 clarification Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000227 grinding Methods 0.000 description 3
- 238000002386 leaching Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229960001866 silicon dioxide Drugs 0.000 description 3
- WKNMKGVLOWGGOU-UHFFFAOYSA-N 2-aminoacetamide;hydron;chloride Chemical compound Cl.NCC(N)=O WKNMKGVLOWGGOU-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000011344 liquid material Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-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
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims (9)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 201110418553 CN102432516B (zh) | 2011-12-14 | 2011-12-14 | 奥拉西坦的精制方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 201110418553 CN102432516B (zh) | 2011-12-14 | 2011-12-14 | 奥拉西坦的精制方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102432516A true CN102432516A (zh) | 2012-05-02 |
CN102432516B CN102432516B (zh) | 2013-10-09 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN 201110418553 Expired - Fee Related CN102432516B (zh) | 2011-12-14 | 2011-12-14 | 奥拉西坦的精制方法 |
Country Status (1)
Country | Link |
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CN (1) | CN102432516B (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102846600A (zh) * | 2012-09-06 | 2013-01-02 | 石药集团欧意药业有限公司 | 一种奥拉西坦药物活性组合物及其制备方法 |
CN104557655A (zh) * | 2013-10-10 | 2015-04-29 | 重庆医药工业研究院有限责任公司 | 一种奥拉西坦的纯化方法 |
CN105348167A (zh) * | 2015-11-11 | 2016-02-24 | 北京万全德众医药生物技术有限公司 | 奥拉西坦的精制方法 |
CN105418475A (zh) * | 2015-12-31 | 2016-03-23 | 山西普德药业股份有限公司 | 一种奥拉西坦的精制工艺 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4686296A (en) * | 1985-07-26 | 1987-08-11 | Denki Kagaku Kogyo Kabushiki Kaisha | Process for producing oxiracetam |
US4788300A (en) * | 1984-04-02 | 1988-11-29 | I.S.F. Societa Per Azioni | Substituted butanamido acetate compounds for the preparation of pyrrolidone derivatives |
US4797496A (en) * | 1984-02-27 | 1989-01-10 | I.S.F. Societa Per Azioni | Process for the preparation of pyrrolidone derivatives |
US4843166A (en) * | 1986-06-26 | 1989-06-27 | Lonza Ltd. | 4-benzyloxy-3-pyrrolin-2-on-1-yl acetamide production |
CN101239938A (zh) * | 2008-03-10 | 2008-08-13 | 苏州凯达生物医药技术有限公司 | (s)-4-羟基吡咯烷酮及其衍生物的制备方法 |
CN101575309A (zh) * | 2009-04-28 | 2009-11-11 | 中国医药集团总公司四川抗菌素工业研究所 | 合成(s)-奥拉西坦的方法 |
-
2011
- 2011-12-14 CN CN 201110418553 patent/CN102432516B/zh not_active Expired - Fee Related
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4797496A (en) * | 1984-02-27 | 1989-01-10 | I.S.F. Societa Per Azioni | Process for the preparation of pyrrolidone derivatives |
US4788300A (en) * | 1984-04-02 | 1988-11-29 | I.S.F. Societa Per Azioni | Substituted butanamido acetate compounds for the preparation of pyrrolidone derivatives |
US4686296A (en) * | 1985-07-26 | 1987-08-11 | Denki Kagaku Kogyo Kabushiki Kaisha | Process for producing oxiracetam |
US4843166A (en) * | 1986-06-26 | 1989-06-27 | Lonza Ltd. | 4-benzyloxy-3-pyrrolin-2-on-1-yl acetamide production |
US4868314A (en) * | 1986-06-26 | 1989-09-19 | Lonza Ltd. | 4-benzyloxy-3-pyrrolin-2-on-1-yl acetamide production |
CN101239938A (zh) * | 2008-03-10 | 2008-08-13 | 苏州凯达生物医药技术有限公司 | (s)-4-羟基吡咯烷酮及其衍生物的制备方法 |
CN101575309A (zh) * | 2009-04-28 | 2009-11-11 | 中国医药集团总公司四川抗菌素工业研究所 | 合成(s)-奥拉西坦的方法 |
Non-Patent Citations (1)
Title |
---|
JESUS F,等: "《New Enantioselective Synthesis of4-Hydrox~2-~xopyrrolidine-N-Acetamide (oxiracetam)from MaIic Acid》", 《TETRAHEDRON ASYMMETRY》 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102846600A (zh) * | 2012-09-06 | 2013-01-02 | 石药集团欧意药业有限公司 | 一种奥拉西坦药物活性组合物及其制备方法 |
CN102846600B (zh) * | 2012-09-06 | 2015-06-17 | 石药集团欧意药业有限公司 | 一种奥拉西坦药物活性组合物及其制备方法 |
CN104557655A (zh) * | 2013-10-10 | 2015-04-29 | 重庆医药工业研究院有限责任公司 | 一种奥拉西坦的纯化方法 |
CN105348167A (zh) * | 2015-11-11 | 2016-02-24 | 北京万全德众医药生物技术有限公司 | 奥拉西坦的精制方法 |
CN105418475A (zh) * | 2015-12-31 | 2016-03-23 | 山西普德药业股份有限公司 | 一种奥拉西坦的精制工艺 |
Also Published As
Publication number | Publication date |
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CN102432516B (zh) | 2013-10-09 |
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Legal Events
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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 | ||
GR01 | Patent grant | ||
C56 | Change in the name or address of the patentee |
Owner name: SHANDONG JINHE DRUG RESEARCH AND DEVELOPMENT CO., Free format text: FORMER NAME: SHANDONG ARURA PHARMACEUTICAL RESEARCH + DEVELOPMENT CO., LTD. |
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CP01 | Change in the name or title of a patent holder |
Address after: 250101 Shandong city of Ji'nan province high tech Zone Shun Road No. 750 University Science Park building D303-1 Patentee after: SHANDONG JINHE DRUG RESEARCH DEVELOPMENT CO.,LTD. Address before: 250101 Shandong city of Ji'nan province high tech Zone Shun Road No. 750 University Science Park building D303-1 Patentee before: SHANDONG ARURA PHARMACEUTICAL RESEARCH & DEVELOPMENT Co.,Ltd. |
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CP03 | Change of name, title or address | ||
CP03 | Change of name, title or address |
Address after: 250101 Shandong Province Jinan Hi-tech Zone Comprehensive Bonded Zone No. 1 North Section of Gangxing No. 3 Road Jinan Yaogu R&D Platform Area No. 3 Floor 8001 Patentee after: Jinhe Tibetan Medicine (Shandong) Health Industry Co.,Ltd. Address before: 250101 d303-1, University Science Park complex building, 750 Shunhua Road, high tech Zone, Jinan City, Shandong Province Patentee before: SHANDONG JINHE DRUG RESEARCH DEVELOPMENT Co.,Ltd. |
|
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20131009 |