Carbon Dioxide → (S)-3-(3-Fluoro-4-methyl-phenyl)-5-hydroxymethyl-oxazolidin-2-one

Participants

Reaction Steps

A mixture of 3-fluoro-4-methyl-aniline (commercial; 1.25 g, 10 mmol), sat. aq. NaHCO3 (10 mL) and acetone (10 mL) was treated dropwise with benzyl chloroformate (1.70 g, 1.41 mL, 1 eq.). After CO2 evolution ceased, the mixture was partitioned between EA and sat. aq. NaHCO3, the org. layer was dried over MgSO4 and concentrated under reduced pressure. The resulting benzyl carbamate was dissolved in THF (50 mL) and cooled under argon to −78° C. n-BuLi (2.5M in hexanes, 6.45 mL, 1.1 eq.) was added dropwise, and the resulting solution was stirred for 1 h at that temperature. The reaction was then allowed to warm to −15° C. at which (S)-glycidyl butyrate (1.69 mL, 1.1 eq.) was added dropwise. The mixture was stirred at rt overnight. A tip of a spatula of Cs2CO3 was added, and the mixture was stirred at rt for 3 h. NH4Cl and EA were added and the phases were separated. The aq. phase was extracted once more with EA and the combined org. extracts were washed several times with sat. aq. NH4Cl, then with brine, dried over Na2SO4 and concentrated. The resulting orange solid was triturated with EA to afford the title intermediate as a pale yellow solid (1.18 g, 53% yield).

Provenance & Evidence