Hydrochloric Acid → 2-(4-Difluoromethoxybenzyl)phenol

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Reaction Steps

In a nitrogen stream, an n-butyllithium hexane solution (2.71 M, 3.8 mL) was added dropwise to a solution of 1-benzyloxy-2-bromobenzene (2.5 g, 9.5 mmol) in THF (90 mL) at −78° C. and the mixture solution was stirred at the same temperature for 30 minutes. To this solution, a solution of 4-difluoromethoxybenzaldehyde (1.23 mL, 1.86 mmol) in THF (30 mL) was added dropwise at −78° C. The reaction mixture was stirred at the same temperature for two hours, and then water was added thereto and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and dried (anhydrous magnesium sulfate), and then the solvent was distilled under reduced pressure and the obtained residue was treated by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:5)] to obtain a crude product. To a solution of the obtained crude product in methanol (26.8 mL), a 20% palladium hydroxide catalyst (147 mg) was added and furthermore concentrated hydrochloric acid (0.4 mL) was added thereto. The mixture solution was stirred under a hydrogen atmosphere for 24 hours, and then the catalyst was filtered off. The solvent was distilled under reduced pressure and the obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:5)] to obtain the title compound (1.03 g, 42%).

Provenance & Evidence