2-Methoxyphenylacetic acid → (4S,5S)-4-methyl5-Phenyl-3-(2-methoxyphenylacetyl)-2-oxazolidinone

Participants

Reaction Conditions

Reaction Steps

9.38 g of 2-methoxyphenylacetic acid are added at room temperature to a suspension of 1.89 g of sodium hydride (80% dispersion in petroleum jelly) in 200 cm3 of dry tetrahydrofuran. This suspension is cooled to −30° C., 7.77 cm3 of pivaloyl chloride are added and then a solution, cooled to −78° C., obtained by adding a solution of 35.27 cm3 of 1.6M butyllithium in hexane to a solution, cooled to −78° C., of 10 g of (4S,5S)-4-methyl-5-phenyloxazolidin-2-one in 200 cm3 of dry tetrahydrofuran is finally added. The reaction mixture is stirred for 45 minutes at −30° C. and then, after returning to room temperature, 200 cm3 of a saturated aqueous ammonium chloride solution and then 500 cm3 of ethyl acetate are added; after separating by settling, the organic phase is washed twice with 100 cm3 of water and then twice with 100 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (particle size 0.04-0.06 mm, diameter 4.8 cm, height 36 cm), eluting under a pressure of 0.6 bar of nitrogen with a mixture of cyclohexane and ethyl acetate (85/15 and then 80/20 by volume) and collecting 50 cm3 fractions. Fractions 14 to 31 are combined and concentrated to dryness under reduced pressure (2.7 kPa). There are obtained 13.6 g of (4S,5S)-4-methyl-5-phenyl-3-(2-methoxyphenylacetyl)oxazolidin-2-one in the form of a yellow oil.

Provenance & Evidence