CN103183602A - 2,2-二丙基丙二酸的结晶方法 - Google Patents
2,2-二丙基丙二酸的结晶方法 Download PDFInfo
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- CN103183602A CN103183602A CN201110457073XA CN201110457073A CN103183602A CN 103183602 A CN103183602 A CN 103183602A CN 201110457073X A CN201110457073X A CN 201110457073XA CN 201110457073 A CN201110457073 A CN 201110457073A CN 103183602 A CN103183602 A CN 103183602A
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- Prior art keywords
- solvent
- propanedioic acid
- dipropyl
- crude product
- dipropyl propanedioic
- 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.)
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- DIRSQLKNZQKDBK-UHFFFAOYSA-N 2,2-dipropylpropanedioic acid Chemical compound CCCC(C(O)=O)(C(O)=O)CCC DIRSQLKNZQKDBK-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 238000000034 method Methods 0.000 title claims abstract description 32
- 239000002904 solvent Substances 0.000 claims abstract description 86
- 238000002425 crystallisation Methods 0.000 claims abstract description 23
- 239000003960 organic solvent Substances 0.000 claims abstract description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 24
- 239000012043 crude product Substances 0.000 claims description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- 230000008025 crystallization Effects 0.000 claims description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 claims description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 3
- 238000005352 clarification Methods 0.000 claims description 3
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 230000001376 precipitating effect Effects 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229960000604 valproic acid Drugs 0.000 description 8
- 239000003814 drug Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 6
- 239000012046 mixed solvent Substances 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- NIJJYAXOARWZEE-UHFFFAOYSA-N Valproic acid Chemical compound CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 238000003810 ethyl acetate extraction Methods 0.000 description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 208000017194 Affective disease Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- FPLYNRPOIZEADP-UHFFFAOYSA-N octylsilane Chemical group CCCCCCCC[SiH3] FPLYNRPOIZEADP-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims (10)
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CN201110457073.XA CN103183602B (zh) | 2011-12-30 | 2011-12-30 | 2,2-二丙基丙二酸的结晶方法 |
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CN201110457073.XA CN103183602B (zh) | 2011-12-30 | 2011-12-30 | 2,2-二丙基丙二酸的结晶方法 |
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CN103183602A true CN103183602A (zh) | 2013-07-03 |
CN103183602B CN103183602B (zh) | 2015-08-12 |
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CN201110457073.XA Expired - Fee Related CN103183602B (zh) | 2011-12-30 | 2011-12-30 | 2,2-二丙基丙二酸的结晶方法 |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107954858A (zh) * | 2017-12-13 | 2018-04-24 | 天津大学 | 一种十一烷二酸的晶型及其制备方法 |
CN112142588A (zh) * | 2020-10-22 | 2020-12-29 | 湖南省湘中制药有限公司 | 一种2-丙基丙二酸的回收及其制备丙戊酸的方法 |
CN112903832A (zh) * | 2019-12-04 | 2021-06-04 | 四川科瑞德制药股份有限公司 | 一种二丙基丙二酸相关杂质的检测方法 |
CN112972449A (zh) * | 2019-12-18 | 2021-06-18 | 四川科瑞德制药股份有限公司 | 一种安全性高的药物组合物及其制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1323288A (zh) * | 1998-09-14 | 2001-11-21 | 罗狄亚纤维与树脂中间体公司 | 羧酸的结晶方法 |
CN1365348A (zh) * | 1999-08-04 | 2002-08-21 | 科金斯公司 | 纯化多元羧酸的方法 |
CN102211994A (zh) * | 2010-04-06 | 2011-10-12 | 上海药明康德新药开发有限公司 | 3-(2-溴苯基)丙酸的工业化合成方法 |
CN102241582A (zh) * | 2010-05-10 | 2011-11-16 | 山东方明药业股份有限公司 | 一种丙戊酸钠的合成工艺 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CS249863B1 (en) * | 1984-08-13 | 1987-04-16 | Jozef Nevydal | Method of dipropylmalonic acid preparation |
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2011
- 2011-12-30 CN CN201110457073.XA patent/CN103183602B/zh not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1323288A (zh) * | 1998-09-14 | 2001-11-21 | 罗狄亚纤维与树脂中间体公司 | 羧酸的结晶方法 |
CN1365348A (zh) * | 1999-08-04 | 2002-08-21 | 科金斯公司 | 纯化多元羧酸的方法 |
CN102211994A (zh) * | 2010-04-06 | 2011-10-12 | 上海药明康德新药开发有限公司 | 3-(2-溴苯基)丙酸的工业化合成方法 |
CN102241582A (zh) * | 2010-05-10 | 2011-11-16 | 山东方明药业股份有限公司 | 一种丙戊酸钠的合成工艺 |
Non-Patent Citations (1)
Title |
---|
潘鹤林等: "多用途的丙二酸二乙酯", 《化工进展》, no. 3, 31 December 1997 (1997-12-31), pages 35 - 38 * |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107954858A (zh) * | 2017-12-13 | 2018-04-24 | 天津大学 | 一种十一烷二酸的晶型及其制备方法 |
CN112903832A (zh) * | 2019-12-04 | 2021-06-04 | 四川科瑞德制药股份有限公司 | 一种二丙基丙二酸相关杂质的检测方法 |
CN112903832B (zh) * | 2019-12-04 | 2022-10-28 | 四川科瑞德制药股份有限公司 | 一种二丙基丙二酸相关杂质的检测方法 |
CN112972449A (zh) * | 2019-12-18 | 2021-06-18 | 四川科瑞德制药股份有限公司 | 一种安全性高的药物组合物及其制备方法 |
CN112142588A (zh) * | 2020-10-22 | 2020-12-29 | 湖南省湘中制药有限公司 | 一种2-丙基丙二酸的回收及其制备丙戊酸的方法 |
CN112142588B (zh) * | 2020-10-22 | 2022-01-28 | 湖南省湘中制药有限公司 | 一种2-丙基丙二酸的回收及其制备丙戊酸的方法 |
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CN103183602B (zh) | 2015-08-12 |
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Address after: 100871, Beijing, Haidian District, Cheng Fu Road, No. 298, Zhongguancun Fangzheng building, 5 floor Patentee after: PEKING UNIVERSITY FOUNDER GROUP Co.,Ltd. Patentee after: PKUCARE PHARMACEUTICAL R&D CENTER Patentee after: PKU HEALTHCARE INDUSTRY Group Address before: 100871, Beijing, Haidian District, Cheng Fu Road, No. 298, Zhongguancun Fangzheng building, 5 floor Patentee before: PEKING UNIVERSITY FOUNDER GROUP Co.,Ltd. Patentee before: PKUCARE PHARMACEUTICAL R&D CENTER Patentee before: Pku Healthcare Industry Group Co.,Ltd. |
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Effective date of registration: 20221013 Address after: 3007, Hengqin international financial center building, No. 58, Huajin street, Hengqin new area, Zhuhai, Guangdong 519031 Patentee after: New founder holdings development Co.,Ltd. Patentee after: PKUCARE PHARMACEUTICAL R&D CENTER Patentee after: Peking University Medical Management Co.,Ltd. Address before: 100871, Beijing, Haidian District, Cheng Fu Road, No. 298, Zhongguancun Fangzheng building, 5 floor Patentee before: PEKING UNIVERSITY FOUNDER GROUP Co.,Ltd. Patentee before: PKUCARE PHARMACEUTICAL R&D CENTER Patentee before: PKU HEALTHCARE INDUSTRY Group |
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