Title:
PROCESS FOR PREPARING DAPAGLIFLOZIN EUTECTIC MATTER
Document Type and Number:
WIPO Patent Application WO/2017/206808
Kind Code:
A1
Abstract:
Provided is a process for preparing a dapagliflozin eutectic, comprising: 1) using a 4-chloro-3-(4-ethoxybenzyl)phenyl halide 6 as a raw material, reacting 6 with lithium alkylide and a zinc salt via an X/Li/Zn exchange reaction in an appropriate solvent to prepare an organozinc reagent - bis[4-chloro-3-(4-ethoxybenzyl)phenyl]zinc, and then reacting same with 2,3,4,6-tetra-O-pivaloyl-α-D-bromoglucopyranose 4 by a nucleophilic substitution reaction to prepare a compound 3; and 2) removing the pivaloyl protecting group of the compound 3 to obtain dapagliflozin 2, and directly reacting same with (S)-1,2-propanediol and water in an appropriate solvent to prepare a dapagliflozin eutectic 1. The synthetic route is as follows: formula (I). In the formula, X in the 4-chloro-3-(4-ethoxybenzyl)phenyl halide 6 is selected from Br or I. The reagents used are all conventional bulk reagents, cheap and easily accessible, the route is simplified, the route cost is greatly reduced, the product yield and purity are relatively high, and the products do not contain diastereoisomers, and are suitable for industrial production.
Inventors:
MA SHUAI (CN)
PAN JING (CN)
LIU ZHENREN (CN)
ZHOU WEICHENG (CN)
PAN JING (CN)
LIU ZHENREN (CN)
ZHOU WEICHENG (CN)
Application Number:
PCT/CN2017/086106
Publication Date:
December 07, 2017
Filing Date:
May 26, 2017
Export Citation:
Assignee:
SHANGHAI INST OF PHARMACEUICAL INDUSTRY (CN)
CHINA STATE INST PHARM IND (CN)
CHINA STATE INST PHARM IND (CN)
International Classes:
C07D309/10; A61K31/70; A61P3/10
Foreign References:
| CN101479287A | 2009-07-08 | |||
| CN104496952A | 2015-04-08 | |||
| CN105153137A | 2015-12-16 |
Other References:
CHEN DEJIN ET AL., CHINA MASTER'S THESES FULL-TEXT DATABASE, ENGINEERING TECHNOLOGY I, vol. B016-731, no. 3, 15 March 2016 (2016-03-15)
LEMAIRE S. ET AL.: "Stereoselective C-Glycosylation Reactions with Arylzinc Reagents", ORGANIC LETTERS, vol. 14, no. 6, 2 March 2012 (2012-03-02), pages 1480 - 1483, XP055069093
LEMAIRE S. ET AL.: "Stereoselective C-glycosylation of furanosyl halides with arylzinc reagents", PURE APPL. CHEM., vol. 86, no. 3, 4 March 2014 (2014-03-04), pages 329 - 333
LEMAIRE S. ET AL.: "Stereoselective C-Glycosylation Reactions with Arylzinc Reagents", ORGANIC LETTERS, vol. 14, no. 6, 2 March 2012 (2012-03-02), pages 1480 - 1483, XP055069093
LEMAIRE S. ET AL.: "Stereoselective C-glycosylation of furanosyl halides with arylzinc reagents", PURE APPL. CHEM., vol. 86, no. 3, 4 March 2014 (2014-03-04), pages 329 - 333
Attorney, Agent or Firm:
HFG LAW & INTELLECTUAL PROPERTY CONSULTING CO., LTD. (CN)
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