反应详情

温度

-78 °C

4-[5-Methyl-4-phenylisoxazol-3-yl]bromobenzene from Step 3 (1.73 g, 5.5 mmol) and tetrahydrofuran (100 mL) were stirred at -78° C. under nitrogen. Butyllithium (1.6M in hexanes, 4.1 mL, 6.6 mmol) was added dropwise, maintaining the temperature below -60° C. After stirring at -78° C. for 0.5 hour, sulfur dioxide gas was passed through a stainless steel needle above the surface of the solution. After 1 minute, the solution changed color from orange to clear, and after 10 minutes pH paper indicated an acidic reaction. Gas addition was ceased and the cooling bath was removed. After 1 hour, the mixture was concentrated to 25 mL and hexane (100 mL) was added. A white precipitate formed which was isolated by filtration. This solid was dissolved in water (50 mL) and sodium acetate (4.5 g, 55 mmol), and hydroxylamine-O-sulfonic acid (0.75 g, 6.6 mmol) were added. The resulting mixture was stirred at room temperature overnight and extracted with ethyl acetate (2×50 mL). The combined extract was washed with brine, dried over MgSO4, and concentrated. A white solid was recrystallized from dichloromethane/hexane (0.8 g, 46%): mp 150.9°-152.3° C. 1H NMR (acetone-d6 /300 MHz) 7.9 (d, J=9.7 Hz, 2H), 7.6 (d, J=9.7 Hz, 2H), 7.4 (m, 3H), 7.3 (m, 2H), 6.7 (bs, 2H), 2.5 (s, 3H). Anal. Calc'd. for C16H14N2O3S: C, 61.13; H, 4.49; N, 8.91. Found: C, 61.18; H, 4.52; N, 8.85. High resolution mass spectrum calc'd. (M+H): 315.0803. Found : 315.0793.

1. temperaturemaintaining the temperature below -60° C
2. waitAfter 1 minute
3. customafter 10 minutes
4. customan acidic reaction
5. additionGas addition
6. customthe cooling bath was removed
7. waitAfter 1 hour
8. concentrationthe mixture was concentrated to 25 mL and hexane (100 mL)
9. additionwas added
10. customA white precipitate formed which
11. customwas isolated by filtration
12. stirringThe resulting mixture was stirred at room temperature overnight
13. extractionextracted with ethyl acetate (2×50 mL)
14. extractionThe combined extract
15. washwas washed with brine
16. dry with materialdried over MgSO4
17. concentrationconcentrated
18. customA white solid was recrystallized from dichloromethane/hexane (0.8 g, 46%)