3-Chloro-1-propanol → 3-(3,5-Difluorophenoxy)propan-1-ol

Participants

Reaction Steps

2.77 g (69.18 mmol) of sodium hydride (60% in mineral oil) were dissolved in 80 ml of DMF. At 0° C., 7.50 g (57.65 mmol) of 3,5-difluorophenol in 15 ml of DMF were added dropwise and, after the gas evolution subsided, the mixture was stirred at RT for 30 min. The solution was cooled to 0° C., 5.45 g (57.65 mmol) of 3-chloro-1-propanol in 15 ml of DMF were added, and the mixture was then stirred at 60° C. for 2 h and at 75° C. for 16 h. The precipitated salts were filtered off, and DMF was removed in a rotary evaporator. The residue was taken up in water and extracted twice with diethyl ether. The combined organic phases were washed successively with water, 1N aqueous sodium hydroxide solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the solvents were removed in vacuo. The crude product was purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate gradient) to result in 8.15 g (75% of theory) of the title compound.

Provenance & Evidence