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Updated: Aug 14, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Simple, rapid procedure for the synthesis of chloromethyl methyl ether and other chloro alkyl ethers
Martin A Berliner1, Katherine Belecki
1Chemical Research and Development, Pfizer Global Research and Development, Groton Labs, Groton, Connecticut 06340, USA. martin.a.berliner@pfizer.com
Abstract:
[Reaction: see text]. Zinc(II) salts catalyze the reaction between acetals and acid halides to provide haloalkyl ethers in near-quantitative yield. Reactions from millimole to mole scale are typically complete in 1-4 h with 0.01 mol % catalyst. The solutions of haloalkyl ethers thus obtained can be utilized directly in reactions in which the presence of the ester byproduct does not interfere. Excess haloalkyl ether is destroyed on workup, thereby minimizing exposure to this class of carcinogenic compounds.
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