Reaction #964378

Reaction equation

n-butyllithium

tert-butyl(4-methylphenyl)acetate

5-bromo-1,1,1-trifluoro-3-methylpentane

ammonium chloride

oxygen

diisopropylamine

→

tert-Butyl 6,6,6-trifluoro-4-methyl-2-(4-methylphenyl)hexanoate

Solvents

ethyl acetate

hexane

THF

cyclohexane ethyl acetate

THF

Conditions

Workup

1. 1
   TemperatureThe reaction solution was then warmed to −10° C.
2. 2
   TemperatureThe reaction solution was then once more cooled to −78° C.
3. 3
   workup.ADDITIONwere added slowly
4. 4
   TemperatureThe reaction solution was then slowly warmed to −30° C.
5. 5
   Temperatureonce more cooled to −78° C
6. 6
   workup.ADDITIONAfter the addition
7. 7
   Temperaturethe solution was slowly warmed to room temperature
8. 8
   workup.STIRRINGstirred overnight
9. 9
   ExtractionThe aqueous phase was extracted twice with ethyl acetate
10. 10
    DryingThe combined organic phases were dried over sodium sulfate
11. 11
    FiltrationAfter filtration
12. 12
    Otherthe solvent was removed under reduced pressure
13. 13
    OtherThe crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 20:1)

Procedure

Under exclusion of oxygen, 0.44 ml (3.2 mmol) of diisopropylamine was initially charged in 4 ml of THF, the mixture was cooled to −78° C. and 1.28 ml (3.2 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 500 mg (2.32 mmol) of tert-butyl(4-methylphenyl)acetate, dissolved in 6 ml of THF, were 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, 596 mg (2.91 mmol) of 5-bromo-1,1,1-trifluoro-3-methylpentane were 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 20:1). This gave 490 mg (1.48 mmol, 61% of theory) of a yellowish oil.

Source