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 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. 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 kieselguhr
10. washthe residue was washed repeatedly with ethyl acetate and dichloromethane
11. concentrationthe combined filtrates were concentrated under reduced pressure

ORDレコード

ord-874a5d5cd98340bca5fed2471a724544

出典データセット

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08796335B2