反应详情

温度

-20 °C

81.5 ml (81.5 mmol) of a 1 M solution of lithium hexamethyldisilazide in toluene were cooled to −20° C., and a solution of 10.0 g (50.3 mmol) of ethyl (3R)-4,4,4-trifluoro-3-methylbutanoate in 50 ml of abs. toluene was added dropwise. The mixture was stirred for 10 min At −20° C., a solution, prepared beforehand, of 14.8 g (70.6 mmol) of 1-bromo-4-chloro-2-fluorobenzene, 366 mg (1.63 mmol) of palladium(II) acetate and 1.35 g (3.42 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl in 50 ml of abs. toluene was then added dropwise. After the addition had ended, cooling was removed and the resulting reaction mixture was initially stirred at RT for 1 h and then at 80° C. overnight. After cooling, the mixture was filtered through celite, the residue was washed repeatedly with toluene and the filtrate obtained was concentrated under reduced pressure. The residue gave, after chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 100:1→100:4), 4.26 g of the title compound (25.1% of theory).

1. customa solution, prepared beforehand
2. additionAfter the addition
3. temperaturecooling
4. customwas removed
5. customthe resulting reaction mixture
6. stirringwas initially stirred at RT for 1 h
7. customat 80° C.
8. customovernight
9. temperatureAfter cooling
10. filtrationthe mixture was filtered through celite
11. washthe residue was washed repeatedly with toluene
12. customthe filtrate obtained
13. concentrationwas concentrated under reduced pressure
14. customThe residue gave