Hydrogen Bromide → HCID 22473580, compound

Participants

Reaction Conditions

Reaction Steps

A warm solution of 3′-amino-4′-fluorobiphenyl-2-carbonitrile (4.24 g, 20 mmol) in 1,4-dioxane (30 ml) was treated with 48% hydrobromic acid (100 ml) and the resulting suspension stirred and cooled to 3° C. (internal temp). A solution of sodium nitrite (1.59 g, 23 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 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 sulfite and saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification on silica, eluting with isohexane on a gradient of ethyl acetate (2-12%) afforded 3′-bromo-4′-fluorobiphenyl-2-carbonitrile as a white solid (2.5 g, 45%): δH (400 MHz, CDCl3) 7.22-7.27 (1H, m), 7.45-7.53 (4H, m), 7.66 (1H, td, J 8 and 2), 7.73 (1H, dd, J 8 and 2), 7.77 (1H, dd, J 8 and 2).

Provenance & Evidence