Transformation of anionically activated trifluoromethyl groups to heterocycles under mild aqueous conditions
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Updated: Jun 3, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Jennifer X Qiao1, Tammy C Wang, Carol Hu
1Research & Development, Bristol-Myers Squibb Company, Princeton, New Jersey 08543, United States. Jennifer.qiao@bms.com
Abstract:
The (hetero)aromatic trifluoromethyl group is present in many biologically active molecules and is generally considered to be chemically stable. In this paper, a convenient one-step synthesis of C-C linked aryl-heterocycles or heteroaryl-heterocycles in good to excellent yields via the reaction of anionically activated trifluoromethyl groups with amino nucleophiles containing a second NH, OH, or SH nucleophile in 1 N sodium hydroxide is reported. The method has high functional group tolerability and is potentially useful in parallel synthesis.
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