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

Participants

Reaction Steps

22.5 ml (22.5 mmol) of a 1 M solution of lithium hexamethyldisilazide in toluene were cooled to −20° C., and a solution of 2.76 g (50.3 mmol) of ethyl (3R)-4,4,4-trifluoro-3-methylbutanoate in 15 ml of abs. toluene was added dropwise. The mixture was stirred for 10 min. At −20° C., a solution, prepared beforehand, of 4.0 g (19.5 mmol) of 2-bromo-5-chlorotoluene, 101 mg (0.45 mmol) of palladium(II) acetate and 371 mg (0.94 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl in 15 ml of abs. toluene was then added dropwise. After the addition had ended, cooling was removed and the resulting reaction mixture was stirred initially at RT for 1 h and then at 100° 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. This gave 3.10 g of the title compound as a crude product which was directly reacted further.

Provenance & Evidence