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CC BY 4.0 · Pharmaceutical Fronts 2021; 03(02): e56-e64
DOI: 10.1055/s-0041-1731757
Original Article

A Novel Telescoped Kilogram-Scale Process for Preparation of Obeticholic Acid

Cheng-Wei Li
1   State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
2   Suzhou Zelgen Biopharmaceuticals Co., Ltd., Kunshan, People's Republic of China
,
Cai Wang
2   Suzhou Zelgen Biopharmaceuticals Co., Ltd., Kunshan, People's Republic of China
,
Chao Guo
2   Suzhou Zelgen Biopharmaceuticals Co., Ltd., Kunshan, People's Republic of China
,
Bin-Hua Lv
2   Suzhou Zelgen Biopharmaceuticals Co., Ltd., Kunshan, People's Republic of China
,
You-Fu Luo
1   State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China
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Abstract

A novel scalable four-step process has been developed to improve the synthesis of obeticholic acid (OCA). The key step of this process was the isolation of the amide intermediate, which underwent hydrogenation, basic epimerization, ketone reduction, and amide hydrolysis in a one-pot procedure. The use of efficient single recrystallization for the final purification in this process made the corresponding work-up procedure more concise and environmentally friendly. A kilogram-scale production of OCA following this process could achieve over 70% yield with all impurities controlled below 0.10%.

Keywords

obeticholic acid - four-step process - amide intermediate - kilogram-scale production

Supplementary Material



Publikationsverlauf

Eingereicht: 19. April 2021

Angenommen: 03. Juni 2021

Artikel online veröffentlicht:
02. September 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
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