CC BY 4.0 · Pharmaceutical Fronts
DOI: 10.1055/s-0042-1750423
Original Article

Industrial-Scale Preparation of a Key Intermediate for the Manufacture of Therapeutic SGLT2 Inhibitors

Lei Huang
1   Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
2   Shanghai Engineering Research Center of Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry Co., Ltd., Shanghai, People's Republic of China
,
Yi Zhang
1   Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
2   Shanghai Engineering Research Center of Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry Co., Ltd., Shanghai, People's Republic of China
,
Xiao-Hui Shan
3   Shandong Shenghua New Material Technology Co., Ltd., Laiyang, People's Republic of China
,
Yu Liu
1   Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
2   Shanghai Engineering Research Center of Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry Co., Ltd., Shanghai, People's Republic of China
,
Jian-Qi Li
1   Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
2   Shanghai Engineering Research Center of Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry Co., Ltd., Shanghai, People's Republic of China
› Author Affiliations

Abstract

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(3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-6-methyltetrahydro-2H-pyran-2-one (1) is a key intermediate for the preparation of promising SGLT2 inhibitors currently undergoing clinical tests for diabetes therapy. However, fewer reports have demonstrated the preparation of compound 1 at an industrial scale. In this article, an efficient preparation of the intermediate for the industrial production was explored from commercially available methyl-α-D-glucopyranoside in seven steps, including TBS protection, benzyl protection, TBS removal, iodination, reduction, demethylation, and oxidation. The batch of the validation process was 42.82 kg with a HPLC purity of 99.31%. The main advantages of this approach are that the total cost is lower than the reported laboratory-scale synthetic method, the quality is reproducible, and the process is safe and environmentally friendly.



Publication History

Received: 23 February 2022

Accepted: 09 May 2022

Article published online:
03 August 2022

© 2022. 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/)

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