反应详情

温度

-78 °C

Into a round bottom flask under nitrogen, diisopropylamine (17.68 g, 174.7 mmol) and 100 mL of anhydrous tetrahydrofuran were added under nitrogen. The solution was cooled to −78° C. and n-butyllithium (1.60 M in hexane, 109.2 mL, 174.7 mmol) was added dropwise, maintaining the temperature at <−70° C., and the reaction was stirred at −78° C. for 1 hour. (2,4-difluoro-phenyl)-carbamic acid benzyl ester (24, 20.00 g, 76.0 mmol) in 100 mL of anhydrous tetrahydrofuran was added dropwise, maintaining the temperature at <−70° C., and the reaction was stirred at −78° C. for 1 hour. Anhydrous dimethylformamide (13.88 g, 190.0 mmol) was added dropwise, maintaining the temperature at <−70° C., and the reaction was stirred at −78° C. for 1 hour, then warmed to room temperature and stirred for 15 minutes. The reaction mixture was poured into 150 mL of water, acidified to pH 1 with 2 M aqueous hydrochloric acid, and extracted with 3×150 mL of ethyl acetate. The organic layers were combined and dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The residue was slurried in hexane, filtered and the solid collected and dried to provide the desired compound (25, 20.69 g, 93%).

1. temperaturemaintaining the temperature at <−70° C.
2. temperaturemaintaining the temperature at <−70° C.
3. stirringthe reaction was stirred at −78° C. for 1 hour
4. temperaturemaintaining the temperature at <−70° C.
5. stirringthe reaction was stirred at −78° C. for 1 hour
6. temperaturewarmed to room temperature
7. stirringstirred for 15 minutes
8. extractionextracted with 3×150 mL of ethyl acetate
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationthe filtrate concentrated under vacuum
12. filtrationfiltered
13. customthe solid collected
14. customdried