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Updated: Apr 12, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Decarboxylative Reissert type trifluoro- and trichloro-methylation of (iso)quinoline derivatives in batch and
M Therkelsen1, M T Rasmussen, A T Lindhardt
1Department of Engineering, Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Finladsgade 22, 8200 Aarhus N, Denmark. lindhardt@eng.au.dk.
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.
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