Methyl iodide → (R)-benzyl 2-((S)-2-oxooxazolidin-4-yl)propanoate

Temperature

-78 °C

To a solution of sodium bis(trimethylsilyl)amide (1M in THF; 68.0 mL) under argon atmosphere was added THF (40.4 mL). The mixture was cooled to −78° C. and a solution of (S)-benzyl 2-(2-oxooxazolidin-4-yl)acetate (7.80 g, 33.2 mmol) in THF (85 mL) was added slowly over ˜15 min. The mixture was stirred for 1 hr at −78° C. and a solution of iodomethane (4.25 mL, 68.0 mmol) in THF (40.4 mL) was added slowly over ˜10 min. The reaction mixture was stirred for 1 hr at −78° C. and ˜1 hr at −40° C. The mixture was quenched with saturated aqueous ammonium chloride solution (˜100 mL) and allowed to warm to room temperature. The mixture was extracted with DCM (3×). The combined organic layers were dried over sodium sulfate, filtered off and concentrated under reduced pressure. The residue was purified by column chromatography [SiO2, 220 g, EtOAc/heptane] to provide (R)-benzyl 2-((S)-2-oxooxazolidin-4-yl)propanoate (7.47 g) as a colorless oil. MS m/z 250.1 (M+H)+; Rt-0.65 min. 1H NMR (400 Mhz, DMSO-d6) δ ppm 7.85 (s, 1H), 7.44-7.28 (m, 5H), 5.10 (s, 2H), 4.36 (t, J=1.0 Hz, 1H), 4.11 (dd, J=5.4, 8.9 Hz, 1H), 4.06-3.98 (m, 1H), 2.69 (quin, J=6.9 Hz, 1H), 1.08 (d, J=7.1 Hz, 3H).

1. stirringThe reaction mixture was stirred for 1 hr at −78° C. and ˜1 hr at −40° C
2. customThe mixture was quenched with saturated aqueous ammonium chloride solution (˜100 mL)
3. temperatureto warm to room temperature
4. extractionThe mixture was extracted with DCM (3×)
5. dry with materialThe combined organic layers were dried over sodium sulfate
6. filtrationfiltered off
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by column chromatography [SiO2, 220 g, EtOAc/heptane]

ORD record

ord-2fd29d35f770419098f84e0ff3e98d28

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434719B2