反应详情

To 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).

1. customTo an oven dried flask
2. customflushed with nitrogen and acetonitrile (30 mL)
3. additionwas added
4. customThe stirred solution was placed in an oil bath at 50° C. under gentle stream of nitrogen
5. temperatureheated for 5 min
6. temperaturecooled in an ice bath
7. customthe layers were separated
8. extractionThe aqueous layer was extracted with EtOAc (2×100 mL)
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. customevaporated
12. customThe crude material was purified by column chromatography (0% to 25% EtOAc/hexanes gradient)