Simplified Version of the Eschweiler-Clarke Reaction.

The traditional Eschweiler-Clarke reaction is a three-component process involving formaldehyde, amine, and formic acid. In this work, we showed that the reductive potential of formaldehyde was sufficient to provide methylation of secondary amines in the absence of acidic additives. Various acid-sensitive moieties remain intact under developed conditions. The scalability of the elaborated approach was shown for several products. Synthesis of the antifungal agent butenafine demonstrated the preparative utility of the developed approach.