p-Toluenesulfonic acid → (R)-methyl 5-oxo-1-((R)-1-phenylethyl)pyrrolidine-3-carboxylate

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Reaction Steps

To a solution of dimethyl itaconate (25 g, 158 mmol) in methanol (150 ml) was added (R)-1-phenylethylamine (20 ml, 158 mmol) at room temperature. The resulting mixture was stirred for 18 hours and concentrated. The residue was dissolved in toluene (100 ml) and p-toluenesulfonic acid (3.0 g, 16 mmol) was added at room temperature. The mixture was refluxed for 16 hours and concentrated. The residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=1/1 to 1/3) to afford methyl (3S)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate as a white solid (14.0 g, 56.5 mmol, 36%) and methyl (3R)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate as a yellow oil (18.7 g, 75.5 mmol, 48%). Each stereochemistry was determined by the data based on the literature (J. Med. Chem. 1990, 33, 71-77).

Provenance & Evidence