Cyclohexane → Ethyl(3R)-2-(4-ethylphenyl)-4,4,4-trifluoro-3-methylbutanoate

24.4 ml (24.4 mmol) of a 1 M solution of lithium hexamethyldisilazide in toluene were cooled to −10° C., and a solution of 3.0 g (16.29 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 −10° C., a solution, prepared beforehand, of 3.92 g (21.18 mmol) of 1-bromo-4-ethylbenzene, 110 mg (0.49 mmol) of palladium(II)acetate and 404 mg (1.03 mmol) of 2′-dicyclohexylphosphino-2-(N,N-dimethylamino)biphenyl in 20 ml of abs. toluene was then added dropwise. The resulting reaction mixture was then stirred first at RT for 1 h and then at 80° C. for 3 h. The mixture was then concentrated under reduced pressure and the residue was taken up in ethyl acetate and added to water. The aqueous phase was re-extracted with ethyl acetate, and the combined organic phases were washed with saturated ammonium chloride solution and saturated sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The residue gave, after chromatography on silica gel (mobile phase first cyclohexane, then gradient cyclohexane/ethyl acetate 200:1→50:1), 3.051 g of the title compound (64.9% of theory, diastereomer ratio about 3:1).

1. customAt −10° C., a solution, prepared beforehand
2. customThe resulting reaction mixture
3. stirringwas then stirred first at RT for 1 h
4. waitat 80° C. for 3 h
5. concentrationThe mixture was then concentrated under reduced pressure
6. additionadded to water
7. extractionThe aqueous phase was re-extracted with ethyl acetate
8. washthe combined organic phases were washed with saturated ammonium chloride solution and saturated sodium chloride solution
9. dry with materialdried over magnesium sulphate
10. concentrationconcentrated under reduced pressure
11. customThe residue gave

ORD record

ord-09be4577481240ae9fb2fd3c957014b3

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09018258B2