反应详情

温度

10 °C

Sodium hydride (1.21 g, 30 mmol, as a 60% suspension in mineral oil) was charged into a round bottom flask equipped with magnetic stirring and a nitrogen blanket, washed twice with 10 mL hexanes, dried of residual hexanes under a nitrogen stream, and suspended in 1,2-dimethoxyethane (20 mL). After cooling in an ice bath to about 10° C., 2-fluoro-6-trifluoromethyl-N-(5, 8-di-methoxy[ 1,2,4]triazolo[1,5-c]pyrimidin-2-yl)benzenesulfonamide (4.21 g, about 98.5% purity, 10 mmol) was added over about 5 min, rinsing in with 1 mL 1,2-dimethoxyethane. A slight exotherm to about 13° C. occurred. Continued ice bath cooling lowered temperature to about 6° C. over about 10 min. To the off-white suspension was added 2,2-difluoroethanol (0.815 niL, 13 mmol) over about 5 min. A slight exotherm to about 13° C. occurred. The light tan suspension was stirred at about 5-10° C. for about 1 hr, then the ice bath was removed. The temperature peaked at about 28° C. (about 2° C. above room temperature) about 0.5 hr later. The tan suspension was stirred overnight (about 20 hr total reaction time), then worked up by addition of the reaction mixture over about 7 min into 5% hydrochloric acid (80 mL, 112 mmol) at about 5-10° C. with ice bath cooling. The suspension was stirred about 18 min at about 9° C., then filtered, washed twice with 15 mL water each, washed twice with 15 mL methanol each, air-dried for about 2 hr, and finally vacuum-dried at about 0.02 mm Hg for about 2 hr over phosphorus pentoxide to afford the product as a white powder (4.34 g, about 92.8% purity, 8.3 mmol, about 83% yield).

1. customequipped
2. washa nitrogen blanket, washed twice with 10 mL hexanes
3. dry with materialdried of residual hexanes under a nitrogen stream
4. washrinsing in with 1 mL 1,2-dimethoxyethane
5. customto about 13° C.
6. temperatureContinued ice bath cooling
7. customto about 6° C.
8. customover about 10 min
9. customto about 13° C.
10. stirringThe light tan suspension was stirred at about 5-10° C. for about 1 hr
11. customthe ice bath was removed
12. custompeaked at about 28° C.
13. custom(about 2° C. above room temperature) about 0.5 hr
14. stirringThe tan suspension was stirred overnight (about 20 hr total reaction time)
15. temperaturecooling
16. stirringThe suspension was stirred about 18 min at about 9° C.
17. filtrationfiltered
18. washwashed twice with 15 mL water each,
19. washwashed twice with 15 mL methanol each,
20. customair-dried for about 2 hr
21. dry with materialfinally vacuum-dried at about 0.02 mm Hg for about 2 hr over phosphorus pentoxide