N-Difluoromethylation of N-pyridyl-substituted anilines with ethyl bromodifluoroacetate
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Updated: Oct 3, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Jindian Duan1,2, Pui Ying Choy3, Kin Boon Gan3
1Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, P.R. China.
Abstract:
A general protocol for N-difluoromethylation of aniline derivatives is developed. Commercially available ethyl bromodifluoroacetate serves as a difluorocarbene source in the presence of a base. This carbene surrogate is attractive owing to its favorable stability, environmental friendliness and inexpensiveness. This reaction system features notable operational simplicity (bench top-grade solvents can be used without any pre-drying and do not require inert atmosphere protection). A wide range of functional groups in aniline derivatives are well-tolerated, and good-to-excellent product yields are generally obtained.
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