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Updated: Mar 21, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Copper-Catalyzed O-Difluoromethylation of Functionalized Aliphatic Alcohols: Access to Complex Organic Molecules with
Kostiantyn Levchenko1, Olexandr P Datsenko1, Oleh Serhiichuk2
1Enamine, Ltd., 78 Chervonotkatska str., 02094 Kyiv, Ukraine.
Abstract:
A two-step synthetic strategy toward difluoromethyl ethers via a CuI-catalyzed reaction of the alcohols, bearing additional protected functionalities, with FSO2CF2CO2H has been developed. The high potential of the developed protocol has been shown by preparing novel OCF2H-analogues of GABA and l-proline. The described transformation has good functional group compatibility and can serve as a powerful synthetic tool for late-stage preparation of complex OCF2H-containing organic compounds as well as building blocks for drug discovery.
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