Title:
METHOD FOR PREPARING DEXIBUPROFEN
Document Type and Number:
WIPO Patent Application WO/2021/047490
Kind Code:
A1
Abstract:
Disclosed in the present invention is a method for preparing dexibuprofen, comprising: (1) after adding toluene into a reaction kettle, adding ibuprofen and n-octyl-d-glucamine, heating to 76 to 80°C, keeping the temperature and reacting for 0.5 h or more, transferring the material into an amine salt crystallization kettle, adding purified water, and then cooling and crystallizing; after decreasing the temperature to 18 to 22°C, centrifuging and separating, washing, and drying to obtain the dexibuprofen n-octyl-d-glucamine salt; the feed ratio of ibuprofen : n-octyl-d-glucamine : toluene : purified water is 1 : 0.65 to 0.75 : 7.5 to 8 : 0.01 to 0.02; (2) performing a hydrolysis reaction to precipitate n-octyl-d-glucamine; (3) performing an acidification reaction to precipitate dexibuprofen. The applicant finally determines that the ratio of the volume of purified water to the weight of ibuprofen in the preparation of amine salt is 0.01 to 0.02L : 1 kg, so that the molar yield of dexibuprofen is finally high, and the melting point of dextro amine salt reaches a qualified standard of 135 to 140°C.
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Inventors:
ZHAO PING (CN)
LIU XIN (CN)
CHENG ZHIGANG (CN)
LIANG QUN (CN)
YANG YIPING (CN)
YANG SHOUSONG (CN)
KONG HULIN (CN)
GUAN QIANQIAN (CN)
CHENG SEN (CN)
ZHOU YONG (CN)
LIAO MINJIE (CN)
LI NING (CN)
ZHANG XUEQIN (CN)
LIU LING (CN)
YANG CIHAI (CN)
LIU XIN (CN)
CHENG ZHIGANG (CN)
LIANG QUN (CN)
YANG YIPING (CN)
YANG SHOUSONG (CN)
KONG HULIN (CN)
GUAN QIANQIAN (CN)
CHENG SEN (CN)
ZHOU YONG (CN)
LIAO MINJIE (CN)
LI NING (CN)
ZHANG XUEQIN (CN)
LIU LING (CN)
YANG CIHAI (CN)
Application Number:
PCT/CN2020/113887
Publication Date:
March 18, 2021
Filing Date:
September 08, 2020
Export Citation:
Assignee:
HUBEI BIOCAUSE HEILEN PHARMACEUTICAL CO LTD (CN)
WUHAN BIOCAUSE PHARMACEUTICAL DEV CO LTD (CN)
WUHAN BIOCAUSE PHARMACEUTICAL DEV CO LTD (CN)
International Classes:
C07C51/02; C07C51/41; C07C51/43; C07C57/30; C07C213/08; C07C215/10
Domestic Patent References:
| WO1996019431A1 | 1996-06-27 |
Foreign References:
| CN110615735A | 2019-12-27 | |||
| KR20030002955A | 2003-01-09 | |||
| CN1490297A | 2004-04-21 |
Other References:
WANG YUCHENG, WANG SUHUI, DAI GUIYUAN, SHI DAQING, CAI PEIJUN: "Isolation and Racemization of Ibuprofen", JOURNAL OF XUZHOU NORMAL UNIVERSITY ( NATURAL SCIENCE EDITION), vol. 16, no. 3, 1 September 1998 (1998-09-01), pages 1 - 2, XP055790095
WANG SHUI; ZHANG PING; SONG ZHIQIAN; DU YIZHEN; QU YIXIN: "Solution thermodynamics ofS-ibuprofenn-octyl-d-glucamine salt in ethanol+water cosolvent mixtures", FLUID PHASE EQUILIBRIA, ELSEVIER, AMSTERDAM NL, vol. 372, 13 April 2014 (2014-04-13), Amsterdam NL, pages 69 - 75, XP029029619, ISSN: 0378-3812, DOI: 10.1016/j.fluid.2014.04.003
XIAO FANGQING, LIU XUTAO, LI RONGDONG: "Preparation of Dexibuprofen", CHINESE JOURNAL OF PHARMACEUTICALS, vol. 31, no. 11, 20 November 2000 (2000-11-20), pages 486, XP009526639, ISSN: 1001-8255
WANG SHUI; ZHANG PING; SONG ZHIQIAN; DU YIZHEN; QU YIXIN: "Solution thermodynamics ofS-ibuprofenn-octyl-d-glucamine salt in ethanol+water cosolvent mixtures", FLUID PHASE EQUILIBRIA, ELSEVIER, AMSTERDAM NL, vol. 372, 13 April 2014 (2014-04-13), Amsterdam NL, pages 69 - 75, XP029029619, ISSN: 0378-3812, DOI: 10.1016/j.fluid.2014.04.003
XIAO FANGQING, LIU XUTAO, LI RONGDONG: "Preparation of Dexibuprofen", CHINESE JOURNAL OF PHARMACEUTICALS, vol. 31, no. 11, 20 November 2000 (2000-11-20), pages 486, XP009526639, ISSN: 1001-8255
Attorney, Agent or Firm:
WUHAN ZHI JIA JOINT INTELLECTUAL PROPERTY AGENCY (GENERAL PARTNERSHIP) (CN)
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