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

Participants

Reaction Conditions

Reaction Steps

To a suspension of 1.89 g of sodium hydride (80% dispersion in petroleum jelly) in 200 cm3 of dry tetrahydrofuran are added at room temperature 9.38 g of 2-methoxyphenylacetic acid. This suspension is cooled to -30° C. and 7.77 cm3 of pivalolyl chloride are added, finally followed by addition of a solution cooled to -78° C. obtained by adding 35.27 cm3 of a 1.6M solution of butyllithium in hexane to a solution, cooled to -78° C., of 10 g of (4S,5S)-4-methyl-5-phenyl-2-oxazolidinone in 200 cm3 of dry tetrahydrofuran. The reaction mixture is stirred for 45 minutes at -30° C., followed, after returning to room temperature, by addition of 200 cm3 of saturated aqueous ammonium chloride solution, and then 500 cm3 of ethyl acetate; after separation of the phases by settling, the organic phase is washed twice with 100 cm3 of water, then twice with 100 cm3 of saturated aqueous sodium chloride solution, and 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 nitrogen pressure of 0.6 bar 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). 13.6 g of (4S,5S)-4-methyl-5-phenyl-3-[(2-methoxyphenyl)acetyl]-2-oxazolidinone are obtained, in the form of a yellow oil.

Provenance & Evidence