Hydrochloric Acid → (2,4-Difluorophenyl)(2-hydroxy-4-methoxyphenyl)methanone

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Reaction Steps

Aluminum chloride (2.03 g, 15.2 mmol) was added in portions to a solution of 1,3-dimethoxybenzene (1.86 mL, 15.2 mmol) and 2,4-difluorobenzoyl chloride (1.86 mL, 15.2 mmol) in 1,2-dichloroethane at 0° C. The mixture was allowed to warm to rt over 3 h then heated at reflux for 6 h. The resultant mixture was allowed to cool to rt, then poured into a mixture of ice (˜100 g) and concentrated hydrochloric acid (˜20 mL). The organic layer was separated. The aqueous solution was stirred at ambient temperature overnight, and extracted with dichloromethane. The organic layers were washed with aqueous sodium bicarbonate and dried over magnesium sulfate. The solvents were evaporated in vacuo to give crude product. A portion of the product was purified by flash chromatography on silica gel, using a gradient of 1%-10% EtOAc/heptane as the eluent to give the title compound 3i (1.8 g). MS: m/z 264.9 (MH+). 1H NMR (CDCl3): δ 3.90 (s, 3H), 6.42 (d of d, 1H, J=9.0 and 2.5 Hz), 6.50 (d, 1H, J=2.5 Hz), 6.91-7.04 (m, 2H), 7.27-7.29 (m, 1H), 7.44-7.50 (m, 1H) and 12.44 (s, 1H).

Provenance & Evidence