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Updated: May 20, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Synthesis of α,α-difluoroethyl aryl and heteroaryl ethers
Eddie Yang1, Matthew R Reese, John M Humphrey
1Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, USA.
Abstract:
Fluorine plays a critical role in modern medicinal chemistry due to its unique properties, and new methods for its incorporation into target molecules are of high interest. An efficient new method for the preparation of aryl-α,α-difluoroethyl ethers (4) via addition of aryl and heteroaryl alcohols (1) to commercially available 2-bromo-1,1-difluoroethene (2) and subsequent hydrogenolysis is presented. This procedure is an attractive alternative to existing methods that employ harshly reactive fluorinating systems such as xenon difluoride and hydrogen fluoride.
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