Title:
METHOD FOR PREPARING HEXAHYDROFURO-FURANOL DERIVATIVE, INTERMEDIATE THEREOF AND PREPARATION METHOD THEREFOR
Document Type and Number:
WIPO Patent Application WO/2019/196263
Kind Code:
A1
Abstract:
The present invention relates to the field of pharmaceutical synthesis, in particular to a method for preparing a hexahydrofuro-furanol derivative, an intermediate thereof and a preparation method therefor. The preparation method comprises steps of a halogenation reaction, an acylation reaction, an enzymatic reduction reaction, a reaction with amine compounds, and a reductive cyclization reaction, (A1, A2, B, Cp1, CL, Cf) wherein R1, R2 and R3 are hydrogen or a hydroxyl protection group; and R4 and R5 are the same or different phenyls, alkyls or substituted phenyls. During the preparation process for the hexahydrofuro-furanol derivative, an enzymatic method is used to construct chirality, and by using such a technical means, products with very high optical purity can be prepared. The preparation method can produce and prepare a key intermediate, (3R, 3aS, 6aR)-hexahydrofuro[2, 3-b]-3-ol, of Darunavir, and is a very economic method suitable for industrial production.
Inventors:
GAO ZHAOBO (CN)
CHEN JIANHUA (CN)
WAN ZHIDONG (CN)
HE DAWEI (CN)
ZHOU ZENGLE (CN)
MA XIAODONG (CN)
XIANG WEI (CN)
LIN JINGXIN (CN)
MEI YIJIANG (CN)
CHEN JIANHUA (CN)
WAN ZHIDONG (CN)
HE DAWEI (CN)
ZHOU ZENGLE (CN)
MA XIAODONG (CN)
XIANG WEI (CN)
LIN JINGXIN (CN)
MEI YIJIANG (CN)
Application Number:
PCT/CN2018/097739
Publication Date:
October 17, 2019
Filing Date:
July 30, 2018
Export Citation:
Assignee:
JIANGSU RUIKE MEDICAL SCIENCE AND TECH CO LTD (CN)
International Classes:
C07C213/06; C07C215/06; C07C215/10; C07C215/12; C07C215/16; C07C217/08; C07C217/76
Domestic Patent References:
| WO2010075887A1 | 2010-07-08 |
Foreign References:
| EP2634180A1 | 2013-09-04 | |||
| CN201810325842A | 2018-04-12 | |||
| CN02817639A | 2002-09-06 | |||
| CN200580010400A | 2005-03-31 | |||
| CN200380010992A | ||||
| EP2634180A1 | 2013-09-04 | |||
| EP2634180A1 | 2013-09-04 |
Other References:
MEKHAEL, M.K.G. ET AL.: "Reactions with 4-Hydroxy-2-Methylbutananilides: Unexpected Formation of a Cyclopropanecarboxamide", HELVETICA CHIMICA ACTA, vol. 94, no. 1, 31 December 2011 (2011-12-31), pages 28 - 37, XP055642618, ISSN: 0018-019X, DOI: 10.1002/hlca.201000370
LESIMPLE, P. ET AL.: "Aluminum Chloride Mediated Aminolysis of Lactones: a General Method for the Preparation of omega-hydroxyalkylamides", SYNTHESIS, 1 April 1991 (1991-04-01), pages 306 - 308, XP055642623, ISSN: 0039-7881
See also references of EP 3778553A4
LESIMPLE, P. ET AL.: "Aluminum Chloride Mediated Aminolysis of Lactones: a General Method for the Preparation of omega-hydroxyalkylamides", SYNTHESIS, 1 April 1991 (1991-04-01), pages 306 - 308, XP055642623, ISSN: 0039-7881
See also references of EP 3778553A4
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