Oxygen → Tert-butyl 5,5,5-trifluoro-2-(4-methylphenyl)pentanoate

Participants

Reaction Conditions

Reaction Steps

With exclusion of oxygen, 0.88 ml (6.3 mmol) of diisopropylamine were 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-butyl-lithium 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 then once more cooled to −78° C. Once 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. The reaction was checked by TLC (mobile phase cyclohexane/ethyl acetate 10:1), after which 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.

Provenance & Evidence