反应详情

温度

-78 °C

Under exclusion of oxygen, 0.88 ml (6.3 mmol) of diisopropylamine was initially charged in 20 ml of THF, the mixture was cooled to −78° C. and 2.52 ml (6.3 mmol) of a 2.5 M solution of n-butyllithium in hexane were added slowly. The reaction solution was then warmed to −10° C. and stirred at this temperature for 10 min. The reaction solution was then once more cooled to −78° C., and 1 g (4.85 mmol) of tert-butyl(4-methylphenyl)acetate, dissolved in 10 ml of THF, was added slowly. The reaction solution was then slowly warmed to −30° C. and subsequently once more cooled to −78° C. After this temperature had been reached, 0.62 ml (5.82 mmol) of 3-bromo-1,1,1-trifluoropropane was slowly added dropwise. After the addition had ended, the solution was slowly warmed to room temperature and stirred overnight. After TLC check (mobile phase cyclohexane/ethyl acetate 10:1), saturated ammonium chloride solution was added and the mixture was taken up in ethyl acetate. The aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate. After filtration, the solvent was removed under reduced pressure. The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 10:1). This gave 542 mg (1.79 mmol, 37% of theory) of a yellowish oil.

1. temperatureThe reaction solution was then warmed to −10° C.
2. temperatureThe reaction solution was then once more cooled to −78° C.
3. additionwas added slowly
4. temperatureThe reaction solution was then slowly warmed to −30° C.
5. temperaturesubsequently once more cooled to −78° C
6. additionAfter the addition
7. temperaturethe solution was slowly warmed to room temperature
8. stirringstirred overnight
9. extractionThe aqueous phase was extracted twice with ethyl acetate
10. dry with materialThe combined organic phases were dried over sodium sulfate
11. filtrationAfter filtration
12. customthe solvent was removed under reduced pressure
13. customThe crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 10:1)