4-Methoxyphenol → 4-(3,5-Difluorophenoxy)anisole

Participants

Reaction Steps

Sodium hydride (7.56 g, 0.189 mol; 60% in oil) was washed with n-hexane to eliminate the oil, and N,N-dimethylformamide (100 ml) was added thereto to make a suspension. To the thus prepared suspension, 4-methoxyphenol (25.84 g, 0.208 mol) was gradually added with stirring, and stirring was continued until the generation of hydrogen gas ceased. 1,3,5-Trifluorobenzene (30.00 g, 0.227 mol) and cuprous chloride (0.50 g) were added thereto. The resultant mixture was heated under reflux for 8 hours with stirring. After allowed to cool, the reaction mixture was poured into ice-water and extracted with toluene. The toluene layer was dried over anhydrous magnesium sulfate. The solvent was removed, and the residual oil was distilled under reduced pressure to give 4-(3,5-difluorophenoxy)anisole (25.42 g). B.P., 98.5° C./0.2 mmHg.

Provenance & Evidence