EDC-promoted one-step synthesis of teriflunomide at the industrial scale

Abstract

Promoted by EDC, the reaction of 5-methylisoxazole-4-carboxylic acid with 4-(trifluoromethyl)aniline could produce the medicine teriflunomide in over 90% yield. In comparison with known methods, this novel production process was reduced to only one step of reaction, free of a chlorinating agent. The reaction could be scaled up to produce 7.5 kg of teriflunomide (yielding 90%, with 99.495% purity), providing a concise and practical method for the synthesis of this well-known medicine. The unique chemical structure of EDC containing an amine moiety endows the molecule with unique properties for promoting the reaction.