Diisopropylethylamine → (4S)-4-(4-methylbenzyl)-1,3-oxazolidin-2-one

Temperature

0 °C

A stirred solution of (2S)-2-amino-3-(4-methylphenyl)propan-1-ol (Step A, 460 mg, 2.79 mmol) in CH2Cl2 (20 mL) at 0° C. was treated with diisopropylethylamine (2.92 mL, 16.74 mmol) and triphosgene (414 mg, 1.39 mmol) under an atmosphere of N2. The reaction stirred at 0° C. for 3 h. The reaction was quenched with sat. NaHCO3 (10 mL) and extracted with EtOAc (4×20 mL). The combined organic layers were washed with brine (25 mL), dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash silica gel chromatography (0-70% EtOAc/hexanes gradient) to afford (4S)-4-(4-methylbenzyl)-1,3-oxazolidin-2-one as a white solid. LCMS=192.2 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.17 (d, J=8 Hz, 2 H), 7.09 (d, J=7.7 Hz, 2 H), 5.39 (br s, 1 H), 4.48 (t, J=8.4 Hz, 1 H), 4.37 (dd, J=8.6, 5.6 Hz, 1 H), 4.11-4.06 (m, 1 H), 2.86 (d, J=7.1 Hz, 2 H), 2.36 (s, 3 H).

1. customThe reaction was quenched with sat. NaHCO3 (10 mL)
2. extractionextracted with EtOAc (4×20 mL)
3. washThe combined organic layers were washed with brine (25 mL)
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe crude product was purified by flash silica gel chromatography (0-70% EtOAc/hexanes gradient)

ORD record

ord-1b530d3c5baa4f108abb922b5394a9cf

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08735435B2