2,2,2-Trifluoroethanol → Sitagliptin

Participants

Reaction Steps

Into a flask was charged [Rh(cod)2]OTf (0.1 mmol) and (S)-Cy2-p-Tol-Biphemp (Ligand E) (0.1 mmol) under a nitrogen atmosphere. Degassed trifluoroethanol was then added (20 mL) and the mixture was stirred at room temperature for 1 h. Into a hydrogenator was charged the enamine amide 2-4 (1 mmol) and then degassed. The catalyst solution was then transferred to the hydrogenator under nitrogen. After degassing three times, the enamine amide was hydrogenated under 100 psig hydrogen gas at 20° C. for 20 h (94% assay yield, 98% ee).

Provenance & Evidence