[F:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5](N)=[C:4]([O:10][CH3:11])[CH:3]=1.N([O-])=O.[Na+].S(=O)(=O)(O)O.[BrH:21]>C(OCC)(=O)C>[Br:21][C:5]1[CH:6]=[C:7]([CH3:8])[C:2]([F:1])=[CH:3][C:4]=1[O:10][CH3:11]A suspension of 4-fluoro-2-methoxy-5-methyl-phenylamine (25.75 g, 0.17 mol) in 180 mL of HBr (48%, 0.9 M) in an ice bath was treated dropwise with an aq solution of sodium nitrite (12.6 g, 0.18 mol, 3.6 M). A brown gas was evolved and the temperature of the reaction was monitored so that the internal temperature did not raise above 10° C. In the meantime, a suspension of CuBr (13.1 g, 0.09 mol) in 6.5 mL of HBr (48%, 13.9 M) was heated to 110° C. Next, the solution at 0° C. was slowly poured (over a period of 20 minutes) into the stirring CuBr suspension. The combined reaction mixture was heated for 2.5 h at 110° C. After cooling to room temperature, the solution was diluted with ethyl acetate and treated with aq sulfuric acid ( 50% v/v). The organic layer was separated and was washed successively with water, sulfuric acid, water, 1.25 M NaOH, water, and saturated aq NaCl. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting brown oil was purified via silica gel flash chromatography (5% ethyl acetate in heptane) to afford 1-bromo-4-fluoro-2-methoxy-5-methyl-benzene (17.1 g, 47%) as a clear liquid: Rf 0.70 (30% ethyl acetate in heptane); 1H NMR (CDCl3, 300 MHz) δ 7.34 (d, J=8.4 Hz, 1H), 6.61 (d, J=10.8 Hz, 1H), 3.85 (s, 3H), 2.18 (d, J=1.8 Hz, 3H); Anal. calcd for C8H8BrFO: C, 43.86. ; H, 3.68; Br, 36.48. Found C, 44.01; H, 3.68; Br, 36.57.
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