反应详情

温度

-40 °C

To a stirred solution of ethyl 4-chloro-6-fluoroquinazoline-2-carboxylate (1.06 g, 4.5 mmol) in THF (15 mL) at −40° C., was added dropwise 1 M 4-fluorophenylmagnesium bromide/THF (5.85 mL, 5.85 mmol). The mixture was stirred at −40° C. for 2 h. The reaction was quenched by adding 0.5 N HCl at 0° C. and then the mixture was extracted with EtOAc (2×20 mL). The solid that precipitated from the combined organic layers was removed by filtration and the filtrate was washed with brine. The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography to afford (4-chloro-6-fluoroquinazolin-2-yl)(4-fluorophenyl)methanone as a solid (950 mg, 69%). 1H NMR (300 MHz, DMSO-d6) δ 8.32-8.36 (m, 1H), 8.13-8.21 (m, 4H), 7.43 (t, J=8.2 Hz, 2H); LC-MS (ESI) m/z 305 (M+H)+.

1. customThe reaction was quenched
2. additionby adding 0.5 N HCl at 0° C.
3. extractionthe mixture was extracted with EtOAc (2×20 mL)
4. customThe solid that precipitated from the combined organic layers
5. customwas removed by filtration
6. washthe filtrate was washed with brine
7. dry with materialThe organic phase was dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by silica gel chromatography