DAST Enabled Synthesis of Fluorinated Amides and Fatty Acid Amides Including Drugs under Ambient Conditions

We present a scalable and workup-free protocol for the synthesis of amides employing equimolar amounts of carboxylic acids and amines with DAST (Diethylaminosulfur trifluoride) in dichloromethane at room temperature. This base-free method accommodates a diverse array of fluorinated aliphatic and aromatic acids, as well as primary, secondary, and electron-deficient amines. The protocol was successfully applied to the synthesis of fatty acid amide derivatives and commercial drugs (e.g., Leflunomide, Ilepcimide, etc.), as well as adaptable to late-stage amidation of more than 10 medicinally relevant building blocks.