反应详情

温度

-78 °C

An oven dried 250 mL 3-neck round bottom flask was fitted with a thermometer, stir bar, septum, and nitrogen inlet. Added 8.02 g (34.7 mmol) of 2-(4-tert-butyl-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole. Established and maintained N2 atmosphere. Added 100 mL of anhydrous THF. Cooled the clear solution to −78°. Stirred rapidly and added 17 mL (43 mmol) of a 2.5 M solution of n-butyllithium in hexane dropwise over 10 minutes. Stirred the clear amber solution at −20° C. for 4 hr. The reaction mixture became red-amber and cloudy. Cooled the mixture to −78° C. Stirred rapidly and added 12 mL of DMF dropwise at a rate to keep the temperature below −60° C. Stirred at −78° C. for 15 min. Stirred at −20° C. for 1 hr. Stirred at room temperature for 1 hr. Quenched with 100 mL of 0.5 M aqueous KHSO4. The aqueous phase was still strongly basic. Added more 1.0 M KHSO4 until the pH was ˜2. Diluted the two phase solution with 300 mL Et2O. Separated phases and extracted the aqueous phase with 100 mL Et2O. Washed the combined organic phases with 200 mL brine and dried over K2CO3. Filtered through 120 g of silica gel and washed through with 300 mL Et2O to remove baseline impurities. Removed the solvent on rotavap to obtain 8.18 g of the title compound as a clear yellow liquid. MS (ESI) 260 (M+H)+.

1. customAn oven dried 250 mL 3-neck round bottom flask
2. customwas fitted with a thermometer
3. temperatureCooled the clear solution to −78°
4. stirringStirred rapidly
5. stirringStirred the clear amber solution at −20° C. for 4 hr
6. stirringStirred rapidly
7. customthe temperature below −60° C
8. stirringStirred at −78° C. for 15 min
9. stirringStirred at −20° C. for 1 hr
10. stirringStirred at room temperature for 1 hr
11. customQuenched with 100 mL of 0.5 M aqueous KHSO4
12. additionAdded more 1.0 M KHSO4 until the pH was ˜2
13. additionDiluted the two phase solution with 300 mL Et2O
14. extractionSeparated phases and extracted the aqueous phase with 100 mL Et2O
15. washWashed the combined organic phases with 200 mL brine
16. dry with materialdried over K2CO3
17. filtrationFiltered through 120 g of silica gel
18. washwashed through with 300 mL Et2O
19. customto remove baseline impurities
20. customRemoved the solvent on rotavap