Acetic Acid → (4R)-3-[(2R)-2-(4-chlorophenyl)propanoyl]-4-isopropyl-1,3-oxazolidin-2-one

Temperature

-78 °C

To a solution of (4R)-3-[(4-chlorophenyl)acetyl]-4-isopropyl-1,3-oxazolidin-2-one (2.80 g, 9.96 mmol) in dry THF (80 mL) at −78° C. under argon, was added dropwise 1.0M solution of NaHMDS in THF (11.0 mL, 11.0 mmol) over a period of 10 min. After stirring at −78° C. for 1 h, Mel (1.9 mL, 30.0 mmol) was added. The resulting reaction mixture was stirred at −78° C. for 1 h and −40° C. for 2 h, quenched with HOAc (30.0 mmol) in ether (20 mL), filtered over celite. The filtrate was concentrated in vacuo and the residue was dissolved in CH2Cl2 (100 mL) and washed with H2O following by brine, dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (5%–10% EtOAc in hexane) to give 1.58 g (5.35 mmol, 54%) of (4R)-3-[(2R)-2-(4-chlorophenyl)propanoyl]-4-isopropyl-1,3-oxazolidin-2-one: 1H NMR (400 MHz, CDCl3) δ 7.30–7.23 (m, 4H), 5.11 (q, 1H, J=7.9 Hz), 4.35 (quintet, 1H, J=3.7 Hz), 4.16–4.09 (m, 2H), 2.46–2.36 (m, 1H), 1.49 (d, 3H, J=7.3 Hz), 0.91 (apparent t, 6H, J=6.9 Hz); ESMS m/e: 296.1 (M+H)+.

1. additionMel (1.9 mL, 30.0 mmol) was added
2. customThe resulting reaction mixture
3. stirringwas stirred at −78° C. for 1 h and −40° C. for 2 h
4. filtrationfiltered over celite
5. concentrationThe filtrate was concentrated in vacuo
6. dissolutionthe residue was dissolved in CH2Cl2 (100 mL)
7. washwashed with H2O following by brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude material was purified by flash chromatography (5%–10% EtOAc in hexane)

ORD record

ord-80788555dd034b6da488b319ce757bc1

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07199135B2