Vigliptin was prepared from (S)-pyrrolidine-2-methonitrile p-toluene sulfonate (W1) and chloroacetyl chloride as starting materials. The key intermediate (S)-1-(2-chloroacetyl) pyrrolidine-2 methonitrile (W2) was prepared by chloroacetylation. After the nucleophilic substitution reaction of W2 and 3-amino-1-amantadyl alcohol, the active drug Vigliptin was prepared. The results showed that the optimal reaction conditions were as follows: the molar ratio of W1 to chloroacetyl chloride and triethylamine was 1∶1.1∶1.2, and W2 could be prepared by reaction at 5 ℃ for about 2 h. The molar ratio of W2 to 3-amino-1-amantadine was 1∶2.0 at 45 ℃ for 12 h to obtain Vigliptin. The chemical structure of the final product was confirmed by IR and its quality was determined by HPLC. The purity was 99.9% and the total yield was 76.5%. The preparation process is easy to operate, mild reaction conditions, high purity and yield, and suitable for industrial production.