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Updated: Jun 14, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Synthesis of tertiary amides from anionically activated aromatic trifluoromethyl groups
Gavin O'Mahony1, Andrew K Pitts
1AstraZeneca R&D Mölndal, Pepparedsleden 1, 43183 Mölndal, Sweden. gavin.omahony@astrazeneca.com
Abstract:
In this paper, a novel synthesis of tertiary amides from anionically activated aromatic trifluoromethyl groups is presented. Anionically activated trifluoromethyl groups react with secondary amines under aqueous conditions to afford tertiary amides. The mechanism involves initial elimination of hydrogen fluoride by an E1cB mechanism to afford an electrophilic quinone methide- or azafulvene-type intermediate that reacts with secondary amines under aqueous conditions to afford the tertiary amide in good yield (up to 99%).
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