Diisopropylethylamine → (4R)-3-[(2S)-3-Methyl-1-oxo-2-[(phenylmethoxy)methyl]butyl]-4-(phenylmethyl)-2-oxazolidinone

Participants

Reaction Steps

To a stirred solution of (R)-4-benzyl-3-(3-methylbutanoyl)oxazolidin-2-one (209 g, 0.80 mol) in absolute CH2Cl2 (3 L) at 0° C. under N2 was added dropwise TiCl4 (92.2 mL, 0.84 mol) over 30 min. After 15 min, DIEA (0.864 mol) was added dropwise over 15 min, and stirring was continued for 1 h at 0° C. ((Chloromethoxy)methyl)benzene (222 mL, 1.60 mol) was added dropwise over 90 min at 0° C. After stirring for 20 h at 0° C., the reaction was quenched by addition of 10% aq NH4Cl (800 mL) and H2O (1 L). The aqueous phase was extracted with CH2Cl2 (2×1 L), and the combined organic layers were washed with brine, dried over MgSO4, and concentrated. The residue was purified by flash chromatography on silica gel to afford (R)-4-benzyl-3-((S)-2-(benzyloxymethyl)-3-methylbutanoyl)oxazolidin-2-one (152 g, 50%). 1H NMR (400 MHz, CDCl3): 0.99 (m, 6H), 2.05 (m, 1H), 2.67 (m, 1H), 3.23 (m, 1H), 3.73 (m, 1H), 3.87 (m, 1H), 4.14 (m, 3H), 4.52 (m, 2H), 4.72 (m, 1H), 7.26 (m, 10H).

Provenance & Evidence