A cost-effective synthetic approach to prepare vildagliptin under gentle experimental conditions has been reported
with good yield and high purity. It was initiated with L-proline via successful reaction with chloroacetyl chloride in
THF (Tetrahydrofuran) to give the 1-(2-chloroacetyl)-pyrrolidine-2-carboxylic acid, which was then treated by TCT (2, 4,
6-trichloro-1, 3, 5-triazine) in DCM (dichloromethane), and converted into 1-(2-chloroacetyl)-pyrrolidine-2-carboxamide,
then further converted into 1-(2-chloroacetyl)-pyrrolidine-2-carbonitrile after dehydrated by TCT in DMF (N, N- dimethylformamide),
the latter product was reacted with 3-aminoadamantanol to get vildagliptin. The total yield of vildagliptin
was about 48%, the purity was about 99%.