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

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.

1. customAt −20° C., a solution, prepared beforehand
2. additionAfter the addition
3. temperaturecooling
4. customwas removed
5. customthe resulting reaction mixture
6. stirringwas stirred initially at RT for 1 h
7. customat 100° 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. customThis gave 3.10 g of the title compound as a crude product which was directly reacted further

ORD-Eintrag

ord-930ead0b35944f9faa85ec66bba4c650

Quelldatensatz

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09018414B2