A facile method to synthesize vildagliptin. Issue 3 (March 2021) - Zhang, Li
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%.