反应详情

温度

0 °C

A solution of n-BuLi (40 mL, 100 mmol) was added dropwise to a solution of diisopropylamine (10.6 g, 105 mmol) in 150 mL of THF at −70° C. The mixture was stirred at 0° C. for 15 minutes and then cooled to −70° C. again. A solution of 4-bromo-3-fluorobenzoic acid (10 g, 45.7 mmol, in 50 mL of THF) was added dropwise. The resulting mixture was stirred at −70° C. for 1 hour then CH2O gas (generated by heating 5.1 g of Para formaldehyde to 200° C.) was bubbled into the mixture. The resulting mixture was stirred at −70° C. for 1 hour then allowed to warm to room temperature and stirred for another 2 hours. HCl gas was bubbled into the suspension for 15 minutes to give a solution. The mixture was diluted with 1 L of EtOAc and washed subsequently with water, saturated Na2CO3 and brine, dried over anhydrous Na2SO4 and concentrated to give 5-bromo-4-fluoro-2-benzofuran-1(3H)-one. 1H-NMR (400 MHz, CDCl3) δ ppm 7.72-7.75 (m, 1H), 7.58 (d, J=8.0 Hz, 1H), 5.36 (s, 2H).

1. temperaturecooled to −70° C. again
2. stirringThe resulting mixture was stirred at −70° C. for 1 hour
3. customCH2O gas (generated by heating 5.1 g of Para formaldehyde to 200° C.) was bubbled into the mixture
4. stirringThe resulting mixture was stirred at −70° C. for 1 hour
5. temperatureto warm to room temperature
6. stirringstirred for another 2 hours
7. customHCl gas was bubbled into the suspension for 15 minutes
8. customto give a solution
9. washwashed subsequently with water, saturated Na2CO3 and brine
10. dry with materialdried over anhydrous Na2SO4
11. concentrationconcentrated