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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence