Benzyl Bromide → 4-(2-Benzyloxyethyl)phenol

Participants

Reaction Steps

To a stirred solution of 2-(4-hydroxyphenyl)ethanol (1.4 g) in tetrahydrofuran (30 ml) was added 60% sodium hydride in mineral oil (405 mg) under ice-cooling, and the mixture was stirred for 1 hour at room temperature. To the stirred reaction mixture was added chloromethyl methyl ether (770 μl) under ice-cooling, and the resulting mixture was stirred for 16 hours at room temperature. Additionally, to the stirred reaction mixture was added 60% sodium hydride in mineral oil (405 mg) under ice-cooling. After the mixture was stirred for 1 hour at room temperature, benzyl bromide (1.2 ml) was added under ice-cooling and the resulting mixture was stirred for 16 hours at room temperature. The reaction mixture was poured into ice-water and extracted with diethyl ether. The extract was washed with brine and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was dissolved in dichloromethane (20 ml), trifluoroacetic acid (20 ml) was added to the solution under ice-cooling with stirring, and the mixture was stirred for 1 hour. After the reaction mixture was concentrated under reduced pressure, 2N aqueous sodium hydroxide solution (20 ml) and water (20 ml) were added to the residue, and the resulting mixture was vigorously shaken. The aqueous layer was separated, washed with diethyl ether, acidified with concentrated hydrochloric acid and extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium bicarbonate solution and brine, and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. Purification of the residue by medium pressure liquid column chromatography on silica gel (eluent: hexane/diethyl ether=2/1) gave 4-(2-benzyloxyethyl)phenol (440 mg).

Provenance & Evidence