A facile method to synthesize vildagliptin. Issue 3 (March 2021)

• Record Type: Journal Article
• Authors: Zhang, Li; Jiang, Lan; Guan, Xiaoshu; Cai, Linhong; Wang, Jingyu; Xiang, Peng; Pan, Junyi; Hu, Xiangnan
• Is Part Of: Journal of chemical research. Volume 45:Issue 3/4(2021)
• Page Start: 305
• Page End: 309
• Publication Date: 2021-03
• Subjects: 3-aminoadamantanol -- central composite design-response surface methodology -- (S)-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile -- synthesis -- vildagliptin; Chemistry -- Research -- Periodicals; Chemistry -- Periodicals; 540.5
• DOI: 10.1177/1747519820967123
• Languages: English
• ISSNs: 1747-5198

Abstract

An efficient and high-yielding synthetic method for the preparation of vildagliptin via four steps is reported. The process starts fromL -proline and involves a successful reaction with chloroacetyl chloride in tetrahydrofuran to afford ( S )-1-(2-chloroacetyl)pyrrolidine-2-carboxylic acid, followed by a reaction with acetonitrile in the presence of sulfuric acid to give ( S )-1-(2-chloroacetyl)pyrrolidine-2-carbonitrile. This is then reacted with 3-aminoadamantanol to give vildagliptin. 3-Aminoadamantanol is prepared from 1-aminoadamantane hydrochloride via oxidation with sulfuric acid/nitric acid and boric acid as the catalyst followed by ethanol extraction. The overall yield is 95%.