Decarboxylative Reissert type trifluoro- and trichloro-methylation of (iso)quinoline derivatives in batch and continuous flow

Abstract

Two decarboxylative methods providing access to N-alkylated α-trihalomethylated heterocyclic amines have been developed. A batch protocol in which methyl trifluoroacetate acts both as a methylating reagent and subsequently as a nucleophilic trifluoromethyl anion precursor upon its addition to (iso)quinoline derivatives. Next, a telescoped continuous flow process, forming the corresponding α-trichloromethylated heterocyclic amines, utilizing a similar decarboxylation of trichloroacetic acid, was developed and taken to scale-up.