Hydrogen Bromide → 3'-BROMO-5'-FLUOROBIPHENYL-2-CARBONITRILE

Participants

Reaction Conditions

Reaction Steps

A warm solution of 5′-amino-3′-fluorobiphenyl-2-carbonitrile (4.5 g, 21 mmol) in 1,4-dioxane (20 ml) was treated with 48% hydrobromic acid (100 ml) and the resulting suspension stirred and cooled to 3° C. (internal temperature). A solution of sodium nitrite (1.7 g, 24 mmol) in water (4 ml) was then added dropwise over 20 min keeping the internal temperature <5° C. Stirring at <5° C. was continued for 2 h before adding a cooled (5° C.) solution of copper(I) bromide (9.1 g, 3 mmol) in 48% hydrobromic acid (30 ml). The resulting purple reaction mixture was stirred at 5° C. for 10 min then warmed to 50° C. for 20 min. The reaction was diluted with ice-cold water (500 ml) and extracted with ethyl acetate (2×200 ml). The organics were combined, washed with 5% aqueous sodium sulphite and saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification on silica, eluting with isohexane (containing 1% methanol) on a gradient of ethyl acetate (5-15%) afforded 5′-bromo-3′-fluorobiphenyl-2-carbonitrile as a white solid (5.52 g, 94%).

Provenance & Evidence