Diisopropylethylamine → tert-butyl (S)-3-((R)-4-benzyl-2-oxooxazolidin-3-yl)-2-(5-chlorothiophen-2-yl)-3-oxopropyl(isopropyl)carbamate

Participants

Reaction Conditions

Reaction Steps

1.0M of titanium tetrachloride in DCM (30.9 mL, 30.9 mmol) was added dropwise to a solution of (R)-4-benzyl-3-(2-(5-chlorothiophen-2-yl)acetyl)oxazolidin-2-one (9.43 g, 28.1 mmol) in DCM (170 mL) at −78° C., followed by N,N-diisopropylethylamine (9.78 mL, 56.2 mmol). The resulting dark blue mixture was stirred at −78° C. for 1 hour. tert-Butyl isopropyl(methoxymethyl)carbamate (11.4 g, 56.2 mmol) was then added. The mixture was stirred at −78° C. for 1 hour, and then allowed to warm up to room temperature. The mixture was stirred at room temperature for 2 hours, quenched with saturated NH4Cl (300 mL), and extracted with DCM (3×200 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The crude product was purified by silica gel chromatography eluting with EtOAc/hexane (0-20%) to give tert-butyl (S)-3-((R)-4-benzyl-2-oxooxazolidin-3-yl)-2-(5-chlorothiophen-2-yl)-3-oxopropyl(isopropyl)carbamate (10.2 g, 72%). MS (APCI+) [M+H]+ 507.2. 1H NMR (CDCl3, 400 MHz) δ 7.36-7.22 (m, 5H), 6.79 (d, J=4.0 Hz, 1H), 6.75 (d, J=4.0 Hz, 1H). 4.67-4.62 (m, 1H), 4.15-4.09 (m, 4H), 3.45-3.38 (m, 2H), 2.80-2.72 (m, 1H), 1.49 (s, 9H), 1.12 (d, J=6.0 Hz, 3H), 1.05 (d, J=6.0 Hz, 3H).

Provenance & Evidence