Synthesis of N-CF ₃ Amides and Ureas from N-CF ₃ Secondary Amines and Acyl Chlorides

A general and traditional strategy for the construction of N -CF 3 secondary amines/ureas from N -CF 3 secondary amines via conventional amide bond formation is developed. This protocol exhibits broad functional group compatibility, straightforward execution, and operates under mild reaction conditions. RCO-OTf was generated in situ in the presence of acyl chlorides and AgOTf as a high reactive intermediate. Three drug-like N -CF 3 amide derivatives, Leflunomide, Phenacetin and Flutolanil, were successfully synthesized, which demonstrated the ability to form N -CF 3 derivatives using N -CF 3 secondary amines as building blocks.