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Updated: Aug 29, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Unexpected migration and oxidative cyclization of substituted 2-acetophenone triflates under basic conditions:
Jotham W Coe1, Krista E Bianco, Brian P Boscoe
1Pfizer Global Research and Development, Groton Laboratories, Pfizer Inc., Groton, Connecticut 06340, USA. coejw@groton.pfizer.com
Abstract:
Oxidative ring closure of alkyl-substituted 2-hydroxyacetophenone trifluoromethanesulfonate esters (triflates) occurs upon exposure to base in anaerobic DMF at 20-90 degrees C. Alkyl substitution is required for ring closure. A migrated enol triflate product forms at lower temperature in high yield via migration of the trifluoromethanesulfonate in the unsubstituted and monoalkyl-substituted cases. The alkyl-substituted enol triflates also enter into the benzofuran-3-one ring-forming process under thermal cyclization conditions. Potential mechanistic pathways are evaluated.
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