Novel and Practical Industrial Process Scale-Up of 5-Bromo-2-chloro-4-(methoxycarbonyl)benzoic acid, a Key Intermediate in the Manufacturing of Therapeutic SGLT2 Inhibitors

Abstract 5-Bromo-2-chloro-4-(methoxycarbonyl)benzoic acid ( 1 ) is a key intermediate for the synthesis of a family of promising SGLT2 inhibitors currently in preclinical and phase I studies for diabetes therapy. In this investigation, cheap, easily available dimethyl terephthalate was used as the r...

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Bibliographic Details
Published in:Pharmaceutical fronts 2022-12, Vol.4 (4), p.e244-e249
Main Authors: Zhang, Yi, Ma, Xiao, Shan, Xiao-Hui, Zhang, Xiao-Wen, Li, Jian-Qi, Liu, Yu
Format: Article
Language:English
Subjects:
5-bromo-2-chloro-4-(methoxycarbonyl)benzoic acid
Original Article
practical process
scale up
sglt2 inhibitors
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Summary:Abstract 5-Bromo-2-chloro-4-(methoxycarbonyl)benzoic acid ( 1 ) is a key intermediate for the synthesis of a family of promising SGLT2 inhibitors currently in preclinical and phase I studies for diabetes therapy. In this investigation, cheap, easily available dimethyl terephthalate was used as the raw starting material, and compound 1 was prepared effectively in six steps, including nitration, hydrolysis, hydrogenation, esterification, bromination, and diazotization. The preparation was run successfully on approximately 70 kg/batch with the total yield of 24%. This practical process was demonstrated to be scalable with a great yield and significant cost reduction.
ISSN:2628-5088
2628-5096
DOI:10.1055/s-0042-1755195