Hydrogen Bromide → 2-Bromo-6-fluorobenzonitrile

Participants

Reaction Conditions

Reaction Steps

2-Amino-6-fluorobenzonitrile (18.0 g, 132 mmol) was dissolved in hot 1,4-dioxane (20 ml), 48% hydrobromic acid (200 ml) was added and the mixture cooled to 0° C. before dropwise addition of sodium nitrite (10.5 g, 152 mmol) in water (20 ml) over 1.5 h. The resulting mixture was stirred at 0° C. for 1.5 h then poured onto a cooled (0° C.) solution of copper(I) bromide (56.8 g, 396 mmol) in 48% hydrobromic acid (50 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 (1200 ml) and extracted with ethyl acetate (2×400 ml). The combined organics were washed with 10% aqueous ammonia solution (400 ml), water (400 ml) and brine (500 ml), dried over anhydrous magnesium sulphate, filtered and evaporated to give an orange oil. Purification by chromatography on silica gel, eluting with isohexane on a gradient of ethyl acetate (2-4%), gave 2-bromo-6-fluorobenzonitrile (18.5 g, 70%) as a white solid: δH (400 MHz, CDCl3) 7.17-7.23 (1H, ddd, J 8, 8 and 1), 7.44-7.52 (2H, m).

Provenance & Evidence