Title:
SYNTHETIC METHOD OF BEMPEDOIC ACID ACTIVE PHARMACEUTICAL INGREDIENT
Document Type and Number:
WIPO Patent Application WO/2022/199378
Kind Code:
A1
Abstract:
The present invention provides a synthetic method of a bempedoic acid active pharmaceutical ingredient. The synthetic method comprises: subjecting an organozinc reagent (a compound 1) and aldehyde (a compound 2) to an addition reaction in an aprotic solvent to generate a compound 3, hydrolyzing the compound 3 under alkaline conditions, and then performing acidification to obtain bempedoic acid. The reaction formula is as shown in the drawing, wherein R is C1-C12 straight-chain or branched-chain alkyl, preferably, R is methyl, ethyl, n-propyl, isopropyl, n-butyl, n-pentyl, and isopentyl, and more preferably, R is methyl or ethyl. Compared with the prior art, the technical solution of the present invention has the advantages of high product purity, high yield, easy purification, etc. The use of the organozinc reagent in preparation of bempedoic acid can greatly reduce reaction by-products and improve the product yield and purity, and the reaction route has low cost and is convenient for industrialization.
Inventors:
RUAN JING (CN)
YAN GONGCHAO (CN)
RUAN XIAONA (CN)
ZHANG WEI (CN)
ZHANG XINXIN (CN)
YAN GONGCHAO (CN)
RUAN XIAONA (CN)
ZHANG WEI (CN)
ZHANG XINXIN (CN)
Application Number:
PCT/CN2022/079806
Publication Date:
September 29, 2022
Filing Date:
March 08, 2022
Export Citation:
Assignee:
SHANGHAI DINGYA PHARMACEUTICAL CHEMICALS CO LTD (CN)
International Classes:
C07C51/347; C07C27/02; C07C59/285
Domestic Patent References:
| WO2020141419A2 | 2020-07-09 | |||
| WO2004067489A2 | 2004-08-12 | |||
| WO2011053892A1 | 2011-05-05 |
Foreign References:
| CN111825546A | 2020-10-27 | |||
| CN111170855A | 2020-05-19 | |||
| CN112479856A | 2021-03-12 | |||
| EP3666750A1 | 2020-06-17 |
Other References:
KINOSHITA YUICHIRO, SHINICHI KANEHIRA, YASUKI HAYASHI, TOSHIRO HARADA: "Catalytic Enantioselective Alkylation of Aldehydes by Using Organozinc Halide Reagents", CHEMISTRY - A EUROPEAN JOURNAL, JOHN WILEY & SONS, INC, DE, vol. 19, no. 10, 5 February 2013 (2013-02-05), DE, pages 3311 - 3314, XP055969264, ISSN: 0947-6539, DOI: 10.1002/chem.201204346
ANDRES, J.M. MARTIN, Y. PEDROSA, R. PEREZ-ENCABO, A.: "Enantioselective reformatsky reaction induced by chiral @b-amino alcohols", TETRAHEDRON, ELSEVIER SIENCE PUBLISHERS, AMSTERDAM, NL, vol. 53, no. 10, 10 March 1997 (1997-03-10), AMSTERDAM, NL , pages 3787 - 3794, XP004105455, ISSN: 0040-4020, DOI: 10.1016/S0040-4020(97)00099-9
ANDRES, J.M. MARTIN, Y. PEDROSA, R. PEREZ-ENCABO, A.: "Enantioselective reformatsky reaction induced by chiral @b-amino alcohols", TETRAHEDRON, ELSEVIER SIENCE PUBLISHERS, AMSTERDAM, NL, vol. 53, no. 10, 10 March 1997 (1997-03-10), AMSTERDAM, NL , pages 3787 - 3794, XP004105455, ISSN: 0040-4020, DOI: 10.1016/S0040-4020(97)00099-9
Download PDF: