Hydrogen Bromide → 5'-Bromo-3,2'-difluorobiphenyl-2-carbonitrile

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Reaction Conditions

Reaction Steps

5′-Amino-3,2′-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 on silica gel eluting with isohexane (containing 0.5% methanol) on a gradient of ethyl acetate (2-6%) gave 5′-bromo-3,2′-difluorobiphenyl-2-carbonitrile (2.48 g, 68%) as a yellow solid: δH (400 MHz, CDCl3) 7.13 (1H, dd, J 9 and 9), 7.27-7.30 (2H, m), 7.53-7.59 (2H, m), 7.64-7.69 (1H, m).

Provenance & Evidence