Sulfuric Acid → Sulfuric Acid

Participants

Reaction Steps

Resolution of (+)-(S)-O-methylmandelic acid. Heat 40.0 g. (0.241 moles) of racemic (±)-α-methyl-α-phenylacetic acid [D. G. Neilson et al J. Chem. Soc., (1962), 1519] with 40.0 g (0.242 moles) of d-ephedrine (available from Aldrich) in 180 mL of 95% ethanol under reflux on a steam bath. Cool the resulting solution to room temperature slowly and leave undisturbed overnight (16 hrs ). Filter the resulting crystallized solid and wash same with 95% ethanol (20 mL) and ethyl ether to give 35 6 g. Recrystallize (twice) the solid from 95% ethanol to give 26.5 g. of salt of d-ephedrine and (+)-α-methoxy-α-phenylacetic acid [(+)-(S)-O-methylmandelic acid], m.p. 185°-188°, [α]D21 +72.8° (c, 4 64, MeOH). Acidify 26.3 g. of the solid with 90 mL of ice-cooled sulfuric acid, with stirring to give a solution. Add sodium chloride (31 g.) and stir the resulting mixture Add 100 mL of dichloromethane to the mixture to give a voluminous precipitate (ephedrine, sulfuric acid salt). Add another 100 mL portion of dichloromethane to the mixture and filter the mixture through a glass filter Wash the solid with 100 mL of dichloromethane. Shake the filtrate and separate the organic and aqueous layers Extract the aqueous layer with 100 ml of dichloromethane. Dry the combined organic layers over anhydrous magnesium sulfate. Evaporate the solvent to give an oil which solidifies on cooling to yield 13.2 g. of the title compound as a solid: m.p. 60.5°-62.0°, [α]D22 +149° (C, 5.61, MeOH).

Provenance & Evidence