A New Route for the Synthesis of the Repaglinide Key Intermediate 3-Ethoxy-4-Ethoxycarbonylphenylacetic Acid. (August 2016)

• Record Type: Journal Article
• Authors: Zhang, Yue; Liu, Tingting; Niu, Zhaohuan; Fu, Yajing; Yang, Jixia; Song, Yongxing; Zhao, Shuchun
• Is Part Of: Journal of chemical research. Volume 40:Number 8(2016)
• Page Start: 506
• Page End: 510
• Publication Date: 2016-08
• Subjects: 3-ethoxy-4-ethoxycarbonylphenylacetic acid -- 3-hydroxyphenylacetic acid -- repaglinide -- intermediate; Chemistry -- Research -- Periodicals; Chemistry -- Periodicals; 540.5
• DOI: 10.3184/174751916X14682401870800
• Languages: English
• ISSNs: 1747-5198

Abstract

A new method is described for manufacturing 3-ethoxy-4-ethoxycarbonylphenylacetic acid, which is a key intermediate of the antidiabetic drug repaglinide, starting from 3-hydroxyphenylacetic acid and involving esterification, formylation, oxidation, etherification and selective hydrolysis. The effect of reaction temperature, time, solvent and substrate ratios on the yield were studied in detail and the optimal conditions are presented in the paper. The new method makes the scale-up operation easier and the environmental problems are fewer. The impurities in the intermediate of the new route were also determined. Characterisation of the product and intermediates involved was achieved by FTIR, 1 H NMR, 13 C NMR, HRMS and DSC.