Hydrochloric Acid → 2,3-Difluoro-6-(1-methylenepropyl)anisole

Participants

Reaction Conditions

Reaction Steps

31.2 g (476 mmol) of zinc dust and 740 mg (2.65 mmol) of lead(II) chloride are suspended in 320 ml of THF and at 0° C. 30 ml (265 mmol) of dibromomethane are added. The mixture is stirred at room temperature for a further 30 minutes and at 0° C. 53 ml (53 mmol) of a 1 M titanium(IV) chloride solution in dichloromethane are added dropwise. The cooling bath is removed and, after an hour, the reaction mixture is cooled to 0° C. again. 10.6 g (53 mmol) of 1-(3,4-difluoro-2-methoxyphenyl)propan-1-one in 106 ml of THF are added dropwise. The reaction mixture is stirred at room temperature for a further hour. It is diluted with diethyl ether and poured cautiously onto a mixture of 4 M hydrochloric acid and ice. The phases are separated, extracted is carried out with diethyl ether, the extracts are washed with saturated sodium chloride solution and dried over sodium sulphate and the solvent is removed. The crude product is purified by column chromatography on silica gel (hexane/diisopropyl ether 20-40%) to give 4.3 g of 2,3-difluoro-6-(1-methylenepropyl)anisole.

Provenance & Evidence