2-Bromo-6-fluorobenzonitrile

Chemical Properties

Off-white crystalline

Uses

2-Bromo-6-fluorobenzonitrile is used as an initial raw material in the synthesis of  2-bromo-6-fluorobenzoic acid.

Synthesis

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 x 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 sulfate, filtered and evaporated to give an orange oil. Purification by chromatography on silica 5 gel eluting with isohexane on a gradient of ethyl acetate (2-4%) gave 2-bromo-6-fluorobenzonitrile. White solid, yield (18.5 g, 70%). δH (400 MHz, CDCl3) 7.17-7.23 (1H, ddd, J 8, 8 and 1), 7.44-7.52 (2H, m).

References

[1] Patent: WO2003/99816, 2003, A1. Location in patent: Page 58
[2] Journal of Heterocyclic Chemistry, 1988, vol. 25, p. 1173 - 1177