反应详情

温度

10 °C

To a solution of 1,3-dibromo-5-fluoro-2-iodobenzene (50 g, 132 mmol) in anhydrous toluene (300 mL) cooled at −35° C. was added a solution of isopropyl-magnesium chloride (84 mL, 171 mmol, 2.0M in Et2O) over 30 minutes while maintaining the internal temperature below −25° C. A clear brown solution was obtained and the stirring was continued for 1.5 h at −25° C. Then anhydrous DMF (34 mL, 436 mmol) was added over a period of 30 minutes. The reaction mixture was warmed to 10° C. (room temperature) over 1 h and stirred at this temperature for 1.5 h (hours). It was then quenched with 3.0M HCl and followed by the addition of ethyl acetate. The organic layer was separated and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with petroleum ether/ethyl acetate (from 50:1 to 20:1) to give 104k as a white solid (20 g, 54%). 1H NMR (500 MHz, CDCl3) δ 10.23 (s, 1H), 7.48 (d, J=7.5, 2H).

1. temperaturewhile maintaining the internal temperature below −25° C
2. customA clear brown solution was obtained
3. customIt was then quenched with 3.0M HCl
4. additionfollowed by the addition of ethyl acetate
5. customThe organic layer was separated
6. customevaporated under reduced pressure
7. customThe residue was purified by silica-gel column chromatography
8. washeluting with petroleum ether/ethyl acetate (from 50:1 to 20:1)