5-Bromo-2-chlorotoluene → Ethyl(3R)-2-(4-chloro-3-methylphenyl)-4,4,4-trifluoro-3-methylbutanoate

Temperature

-10 °C

29.2 ml (29.2 mmol) of a 1 M solution of lithium hexamethyldisilazide in toluene were cooled to −10° C., and a solution of 4.30 g (23.4 mmol) of ethyl (3R)-4,4,4-trifluoro-3-methylbutanoate in 26 ml of abs. toluene was added dropwise. The mixture was stirred for 10 min At −10° C., a solution, prepared beforehand, of 5.0 g (19.5 mmol, 80% pure) of 5-bromo-2-chlorotoluene, 131 mg (0.58 mmol) of palladium(II) acetate and 483 mg (1.23 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl in 26 ml of abs. toluene was then added dropwise. The resulting reaction mixture was initially stirred at RT for 1 h and then at 80° C. for 4 h. After cooling, the mixture was diluted with ethyl acetate, washed twice with sat. aqueous sodium bicarbonate solution and once with sat. sodium chloride solution, dried over sodium sulphate and concentrated under reduced pressure. This gave 7.80 g of the title compound as a crude product which was directly reacted further.

1. customa solution, prepared beforehand
2. customThe resulting reaction mixture
3. stirringwas initially stirred at RT for 1 h
4. waitat 80° C. for 4 h
5. temperatureAfter cooling
6. washwashed twice with sat. aqueous sodium bicarbonate solution and once with sat. sodium chloride solution
7. dry with materialdried over sodium sulphate
8. concentrationconcentrated under reduced pressure
9. customThis gave 7.80 g of the title compound as a crude product which was directly reacted further

ORD record

ord-19995d48ae1d4fa994c5d8125423e647

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09018414B2