反应详情

温度

0 °C

To a clear solution of 2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole from Example 2 (400 mg, 1 mmol) in tetrahydrofuran (THF) (8 mL) at 0° C., n-BuMgCl (2M solution in THF, 2 mL, 4 mmol) was added over 10 minutes. After stirring for additional 10 minutes, ice bath was removed and solution stirred for 1 hour. The reaction mixture was re-cooled to 0° C. and triethylborane (1M solution in THF, 5 mL, 5 mmol) was added. After stirring for 2 hours, the reaction was heated to reflux for 48 hours. The reaction mixture was cooled to room temperature and treated with aqueous sodium acetate (1 g in 4 mL water). After stirring for minutes, solid hydroxylamine-O-sulfonic acid (1 g) was added and the mixture stirred for 20 hours. The reaction mixture was diluted with water and extracted with ether (2×250). The ethereal layer was dried over sodium sulfate, filtered and concentrated in vacuo. The crude solid (568 mg) was purified by chromatography [silica gel, ethyl acetate/toluene (3/7)] to give 4-[2-(4-chlorophenyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide (260 mg, 65%): mp (DSC) 225° C. Anal. Calc'd. for C16H11N3SO2F3Cl: C, 47.83, H, 2.76 N, 10.46, S, 7.98. Found: C, 48.00, H, 2.83, N, 10.14, S, 7.94.

1. customice bath was removed
2. stirringsolution stirred for 1 hour
3. stirringAfter stirring for 2 hours
4. temperaturethe reaction was heated
5. temperatureto reflux for 48 hours
6. temperatureThe reaction mixture was cooled to room temperature
7. stirringAfter stirring for minutes
8. stirringthe mixture stirred for 20 hours
9. extractionextracted with ether (2×250)
10. dry with materialThe ethereal layer was dried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe crude solid (568 mg) was purified by chromatography [silica gel, ethyl acetate/toluene (3/7)]