反应详情

温度

-75 °C

3,5-Dimethylisoxazole (220 g, 2.27 moles) in 2.2 L tetrahydrofuran under nitrogen was cooled with stirring to -75° C. and 908 mL of 2.5M n-butyllithium (2.27 moles) in hexanes were added over 1 hour keeping the temperature at or less than 65° C. The chilled solution was stirred for thirty minutes after addition was complete and was then treated at about -70° C. with a solution of 112 g (2.54 moles) of ethylene oxide in 390 ml tetrahydrofuran over a period of 1.5 hours, keeping the temperature at about -65° C. and stirred overnight. The mixture at 8° C. was quenched with continued cooling in an 8° C. bath by adding 1.2 L of 2.5M hydrochloric acid over a period of 20 minutes, during which time the temperature rose to 23° C., and was stirred for 10 minutes. The organic phase was separated, washed with 500 ml of water and concentrated to give 147 g of title compound as a brown oil. The combined aqueous phases (original+wash phase) were extracted with methyl tert-butyl ether (3×200 ml) and the combined organic extracts were concentrated to give an additional 125 g of title compound as a brown oil.

1. customless than 65° C
2. stirringThe chilled solution was stirred for thirty minutes
3. additionafter addition
4. customat about -65° C.
5. stirringstirred overnight
6. customThe mixture at 8° C. was quenched
7. temperaturewith continued cooling in an 8° C. bath
8. additionby adding 1.2 L of 2.5M hydrochloric acid over a period of 20 minutes
9. customrose to 23° C.
10. stirringwas stirred for 10 minutes
11. customThe organic phase was separated
12. washwashed with 500 ml of water
13. concentrationconcentrated