反应详情

Under argon, 196.9 mg (0.88 mmol) of palladium(II) acetate and 724.8 mg (1.84 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl were initially charged in 50 ml of anhydrous toluene. 43.8 ml (43.8 mmol) of a 1 M solution of lithium hexamethyldisilazide in THF were then added slowly, and the reaction solution was stirred at RT for 10 min. The reaction solution was then cooled to −10° C., 7 g (38.0 mmol) of (+/−)-ethyl 4,4,4-trifluoro-3-methylbutanoate were added slowly and the mixture was stirred at −10° C. for 10 min 5 g (29.2 mmol) of 4-bromotoluene, dissolved in 50 ml of toluene, were then added dropwise, and the reaction solution was warmed initially to RT and then to 80° C. The mixture was stirred at this temperature for 2 h, then cooled to RT and stirred overnight. After the reaction had gone to completion (monitored by TLC; mobile phase cyclohexane/dichloromethane 2:1), the reaction mixture was filtered through kieselguhr, the residue was washed repeatedly with ethyl acetate and dichloromethane and the combined filtrates were concentrated under reduced pressure. The crude product obtained was purified chromatographically on silica gel (mobile phase petroleum ether/dichloromethane 4:1→3:1). This gave 3.91 g (14.3 mmol, 48.8% of theory) of the title compound as a colourless liquid.

1. temperatureThe reaction solution was then cooled to −10° C.
2. additionwere then added dropwise
3. temperaturethe reaction solution was warmed initially to RT
4. customto 80° C
5. stirringThe mixture was stirred at this temperature for 2 h
6. temperaturecooled to RT
7. stirringstirred overnight
8. filtrationthe reaction mixture was filtered through kieselguhr
9. washthe residue was washed repeatedly with ethyl acetate and dichloromethane
10. concentrationthe combined filtrates were concentrated under reduced pressure