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Updated: Feb 18, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Scalable Synthesis of Trifluoromethylated Imidazo-Fused N-Heterocycles Using TFAA and Trifluoroacetamide as
Gabriel Schäfer1, Muhamed Ahmetovic1, Stefan Abele1
1Process Chemistry R&D, Idorsia Pharmaceuticals Ltd. , Hegenheimermattweg 91, CH-4123 Allschwil, Switzerland.
Abstract:
A scalable synthesis of trifluoromethylated imidazo-fused N-heterocyles from heterocyclic benzylamines using TFAA as trifluoromethylating reagent is presented. The reaction proceeds via intermediate benzylic N-trifluoroacetamides followed by dehydrative cyclization to the products. To further broaden the scope and practicality, a new method for the preparation of benzylic N-trifluoroacetamides via alkylation of trifluoroacetamide with benzyl (pseudo)halides was developed. Both methods proceed under mild conditions, and their symbiosis provides access to a wide range of novel CF3-heterocycles.
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