Hydrogen Bromide → 5'-Bromo-5,2'-difluorobiphenyl-2-carbonitrile

Participants

Reaction Conditions

Reaction Steps

5′-Amino-5,2′-difluorobiphenyl-2-carbonitrile (2.87 g, 12.5 mmol) was dissolved in hot 1,4-dioxane (4 ml), 48% aqueous hydrobromic acid (40 ml) was added and the mixture cooled to 0° C. before dropwise addition of sodium nitrite (0.86 g, 12.5 mmol) in water (1.5 ml) over 20 min. The resulting mixture was stirred at 0° C. for 1.5 h then poured onto a cooled (0° C.) solution of copper(I) bromide (5.38 g, 37.5 mmol) in 48% hydrobromic acid (10 ml). The solution was stirred at 0° C. for 15 min then heated at 50° C. for 20 min. The mixture was cooled to ambient temperature, diluted with water (500 ml) and extracted with ethyl acetate (2×300 ml). The combined organics were washed with 10% aqueous ammonia solution (200 ml), water (200 ml) and brine (200 ml), dried over anhydrous magnesium sulfate, filtered and evaporated to give a black solid. Purification by chromatography [silica gel, 2-6% EtOAc/isohexane (containing 0.5% methanol)] gave the title compound as a pale brown solid: 1H NMR (400 MHz, CDCl3) δ 7.13 (1H, dd, J 9, 9 Hz), 7.19-7.23 (2H, m), 7.52-7.60 (2H, m), 7.81 (1H, dd, J 8, 5 Hz).

Provenance & Evidence