反应详情

温度

90 °C

In a 500-mL round-bottomed flask, a mixture of 8-bromo-7-fluoro-3-methylquinoxalin-2(1H)-one (600) (3.57 g, 13.89 mmol) and POCl3 (20.0 mL, 215 mmol) was heated at 90° C. for 1.5 h with a reflux condenser. The reaction mixture was cooled to RT and most of the excess POCl3 was removed under reduced pressure (rotary evaporator). The mixture was treated with EtOAc (100 mL), cooled in an ice bath, treated with ice chips and 1 N NaOH slowly. After phase separation, the organic layer was washed with brine (50 mL), dried over MgSO4, filtered and concentrated to afford the crude product as a brown solid. The crude residue was purified by chromatography on the ISCO Combiflash Rf (80 g Redisep column, using a gradient of 0-100% DCM in hexanes (eluted with ca. 35-60% DCM)) affording 5-bromo-3-chloro-6-fluoro-2-methylquinoxaline (1.88 g, 6.82 mmol, 49% yield) as a light orange crystalline solid. m/z (ESI, +ve ion) 275.0/277.0 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 8.01 (1H, dd, J=9.3, 5.4 Hz), 7.58 (1H, dd, J=9.1, 8.1 Hz), 2.86 (3H, s). 19F NMR (376 MHz, CDCl3) δ ppm −99.07 (1F, s).

1. customwas removed under reduced pressure (rotary evaporator)
2. additionThe mixture was treated with EtOAc (100 mL)
3. temperaturecooled in an ice bath
4. additiontreated with ice chips and 1 N NaOH slowly
5. customAfter phase separation
6. washthe organic layer was washed with brine (50 mL)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto afford the crude product as a brown solid
11. customThe crude residue was purified by chromatography on the ISCO Combiflash Rf (80 g Redisep column