Hydrochloric Acid → (R)-4-(4-Chlorophenyl)pyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, to methanol (220 ml) was added methyl (3S,4R)-4-(4-chlorophenyl)-2-oxopyrrolidine-3-carboxylate (28.0 g, 110 mmol), and 2 mol/L sodium hydroxide aqueous solution (66 ml) was dropped over a period of 1 hour. After completion of dropping, the mixture was further stirred for 1 hour, and neutralized with 2 mol/L hydrochloric acid (71 ml), and methanol was distilled off under reduced pressure. The residue was extracted with ethyl acetate (150 ml×2), to obtain an ethyl acetate solution containing (3S,4R)-4-(4-chlorophenyl)-2-oxopyrrolidine-3-carboxylic acid. This solution was dropped over a period of 4 hours into xylene (150 ml) heated at 130 to 140° C. while distilling off ethyl acetate. After completion of the reaction, xylene (100 ml) was added, and the mixture was filtrated and concentrated under reduced pressure. Crystallization from xylene/heptanes was performed to obtain 19.3 g (98.6 mmol) of a title compound. Yield: 90%. The spectrum data corresponded to the value in non-patent document 1. The optical purity of the resultant title compound was measured by HPLC to find a value of 99% ee.

Provenance & Evidence