N(OC(C)(C)C)=O.[Br:8][C:9]1[CH:10]=[C:11]([O:16][C:17]2[C:22]([F:23])=[C:21]([CH3:24])[CH:20]=[CH:19][C:18]=2N)[CH:12]=[C:13]([Cl:15])[CH:14]=1.[ClH:26].CCOC(C)=O>C(#N)C>[Br:8][C:9]1[CH:10]=[C:11]([O:16][C:17]2[C:22]([F:23])=[C:21]([CH3:24])[CH:20]=[CH:19][C:18]=2[Cl:26])[CH:12]=[C:13]([Cl:15])[CH:14]=1To an oven dried flask was added CuCl2 (4.06 g, 30.2 mmol). The flask was placed under high vacuum, flushed with nitrogen and acetonitrile (30 mL) was added. t-Butyl nitrite (4.50 mL, 37.8 mmol) was added dropwise. The stirred solution was placed in an oil bath at 50° C. under gentle stream of nitrogen, heated for 5 min and a solution of {2-[(3-bromo-5-chlorophenyl)oxy]-3-fluoro-4-methylphenyl}amine in acetonitrile (40 mL) was added dropwise. The reaction was stirred for 0.5 h, cooled in an ice bath and poured into ice cold, aqueous HCl (1 N, 125 mL). EtOAc (100 mL) was added and the layers were separated. The aqueous layer was extracted with EtOAc (2×100 mL). The organic extracts were combined, dried over Na2SO4, filtered and evaporated. The crude material was purified by column chromatography (0% to 25% EtOAc/hexanes gradient) to afford the title compound (3.2 g, 60%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 7.48-7.47 m, 1H), 7.41-7.38 (m, 1H), 7.32-7.28 (m, 1H), 7.11-7.10 (m, 1H), 7.04-7.03 (m, 1H), 2.27 (s, 3H).
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