Hydrogen Bromide → 5-Bromo-2-fluoro-2'-(methylthio)biphenyl

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To a solution of 6-fluoro-2′-(methylthio)biphenyl-3-ylamine (0.3969 g, 1.70 mmol) in 1,4-dioxane (2.1 ml) was added 48% aqueous hydrobromic acid (8 ml) and the mixture was cooled to 3° C. before the dropwise addition of sodium nitrite (0.1365 g, 1.98 mmol) in water (0.5 ml) over 5 min, while the temperature was kept below 5° C. The resulting mixture was stirred at 4±1° C. for 2 h 40 min then more sodium nitrite (0.0255 g, 0.37 mmol) in water (0.1 ml) was added dropwise and the mixture was stirred at 3° C. for 50 min. A cooled (3° C.) solution of copper(I) bromide (0.7443 g, 5.19 mmol) in 48% hydrobromic acid (2.4 ml) was added and the mixture was stirred at 3° C. for 15 min then heated to 50° C. for 1 h. The mixture was cooled to ambient temperature, diluted with water (50 ml) and extracted with ethyl acetate (4×35 ml). The combined organics were washed with 1 M aqueous Na2SO3 solution (30 ml), then saturated aqueous NH4Cl solution (30 ml), dried (MgSO4), and evaporated to give a brown oil. Purification by chromatography (silica gel, 0-2% EtOAc/isohexane) gave 0.2868 g (57%) of the title compound as a white solid: 1H NMR (360 MHz, CDCl3) δ 2.40 (3H, s), 7.04 (1H, t, J 8.8 Hz), 7.16-7.24 (2H, m), 7.32 (1H, d, J 7.7 Hz), 7.36-7.51 (4H, m).

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