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, 2H), 7.09 (d, J=7.7 Hz, 2H), 5.39 (br s, 1H), 4.48 (t, J=8.4 Hz, 1H), 4.37 (dd, J=8.6, 5.6 Hz, 1H), 4.11-4.06 (m, 1H), 2.86 (d, J=7.1 Hz, 2H), 2.36 (s, 3H).

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-45fd215bf89d4459a1ebdc75cc7ec7b5

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07652049B2