4-Bromotoluene → Ethyl 4,4,4-trifluoro-3-methyl-2-(4-methylphenyl)butanoate

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 added slowly, and the reaction solution was then 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 first to RT and then heated to 80° C. The mixture was stirred at this temperature for 2 h and then cooled to RT and stirred overnight. After the reaction had ended (monitored by TLC; mobile phase cyclohexane/dichloromethane 2:1), the reaction mixture was filtered through kiesel-guhr, the residue was washed repeatedly with ethyl acetate and dichloromethane and the combined filtrates 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. stirringthe mixture was stirred at −10° C. for 10 min
3. additionwere then added dropwise
4. temperaturethe reaction solution was warmed first to RT
5. temperatureheated to 80° C
6. stirringThe mixture was stirred at this temperature for 2 h
7. temperaturecooled to RT
8. stirringstirred overnight
9. filtrationthe reaction mixture was filtered through kiesel-guhr
10. washthe residue was washed repeatedly with ethyl acetate and dichloromethane
11. concentrationthe combined filtrates concentrated under reduced pressure

ORD 기록

ord-8056e7c0a0f744a7a549b797aeca90ad

출처 데이터셋

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09018258B2