Hydrogen Bromide → 2-Bromo-3-fluorobenzonitrile

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To a solution of 2-amino-3-fluorobenzonitrile (17.07 g, 0.125 mol) in 1,4-dioxane (20 ml) was added 48% aqueous hydrobromic acid (200 ml) and the solution was cooled to 0° C. before adding dropwise a solution of sodium nitrite (9.95 g, 0.144 mol) in water (22 ml) over 35 min so that the temperature did not rise above 3° C. The resulting mixture was stirred at 2–3° C. for 2 h then poured onto a cooled (5° C.) solution of copper(I) bromide (26.98 g, 0.188 mol) in 48% hydrobromic acid (100 ml). The mixture was stirred for 10 min then heated to 50° C. over 1 h. The mixture was cooled to ambient temperature, diluted with water (1 l) and extracted with diethyl ether (2×500 ml). The combined organic extracts were washed with 1 M aqueous Na2SO3 (500 ml), then saturated aqueous NH4Cl (200 ml), dried (MgSO4), and evaporated to give a brown oil/solid. Purification by chromatography (silica gel, 10% EtOAc/isohexane) and trituration of a mixed fraction with isohexane afforded 13.22 g (53%) of 2-bromo-3-fluorobenzonitrile as a pale yellow solid: 1H NMR (360 MHz, CDCl3) δ 7.62–7.68 (1H, m), 7.74–7.85 (1H, ddd, J 9, 9, 1), 7.74–7.85 (1H, ddd, J 8, 1, 1).

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