Hydrogen Peroxide → 3,5-Difluoro-4-difluoromethoxyphenol

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Reaction Steps

Compound (251) can be prepared in the same manner as in Preparation Example 248, except for replacing 3-fluoro-4-difluoromethoxyphenol with 3,5-difluoro-4-difluoromethoxyphenol. The 3,5-difluoro-4-difluoromethoxyphenol can be obtained by converting 2,6-difluorophenol to a formic ester, fluorinating the ester with DAST, brominating the resulting 2,6-difluoro-1-difluoromethoxybenzene, preparing a Grignard reagent from the resulting 4-bromo-2,6-difluoro-1-difluoromethoxybenzene, and reacting the Grignard reagent with t-butyl hydroperoxide or converting the Grignard reagent to a boric ester, and oxidizing the ester with hydrogen peroxide under a basic condition. Alternatively, 3,5-difluoro-4-difluoromethoxyphenol can also be obtained by nitrating 3,5-difluoro-4-difluoromethoxybenzene, reducing the product to 3-fluoro-4-trifluoromethoxyaniline, and decomposing a diazonium salt of the 3-fluoro-4-trifluoromethoxyaniline in sulfuric acid.

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