Methyl iodide → (4S)-3-{(2S)-1-oxo-2-[3,5-bis(trifluoromethyl)phenyl]propyl}4-(phenylmethyl)-2-oxazolidinone

Temperature

-78 °C

Sodium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 19.3 mL) was added slowly to a stirred, cooled (−78° C.) solution of (4S)-3-[3,5-bis(trifluoromethyl)benzeneacetyl]-4-(phenylmethyl)-2-oxazolidinone (Description 36, 7.25 g, 16.8 mmol) in tetrahydrofuran (60 mL) and the mixture was stirred at −78° C. for 1 hour. Iodomethane (21 mL, 33.6 mmol) was added and the mixture was stirred at −78° C. for 30 minutes, at 0° C. for 1 hour, then at room temperature overnight. Saturated aqueous ammonium chloride was added and the mixture was extracted with ethyl acetate. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane:EtOAc (90:10 increasing to 85:15), to give the title compound as a colorless oil (5.14 g, 69%). 1H NMR (360 MHz, CDCl3) δ 7.84 (2H, s), 7.78 (1H, s), 7.38–7.27 (3H, m), 7.23–7.21 (2H, m), 5.26 (1H, q, J 7.0 Hz), 4.68–4.64 (1H, m), 4.19–4.15 (2H, m), 3.34 (1H, dd, J 3.3, 13.3 Hz), 2.83 (1H, dd, J 9.5, 13.3 Hz), and 1.60 (3H, d, J 7.0 Hz).

1. stirringthe mixture was stirred at −78° C. for 30 minutes, at 0° C. for 1 hour
2. customat room temperature
3. customovernight
4. extractionthe mixture was extracted with ethyl acetate
5. dry with materialThe combined organic fractions were dried (MgSO4)
6. customthe solvent was evaporated under reduced pressure
7. customThe residue was purified by flash column chromatography on silica gel
8. washeluting with isohexane:EtOAc (90:10 increasing to 85:15)

ORD record

ord-1f31d30f1bb44380b99baf81beb5f3d7

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07105507B2