5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid → HCID 57758674, compound

Participants

Reaction Steps

Under stirring by means of an impeller, O-tert-butyl-N,N′-diisopropylurea (3,020 g, 15.00 mol) was added at room temperature to a suspension of 5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid (1,165 g, 4.994 mol) in dichloromethane (10 L). After rising in internal temperature and initiation of reflux had been observed, the mixture was cooled in an ice-water bath. The reaction mixture was cooled to room temperature. Thereafter, the ice-water bath was removed, and the reaction mixture was stirred for 1 hour, and subsequently, for 3 hours under heating at 40° C. The reaction mixture was further stirred for 1 hour with cooling in an ice-water bath, and insoluble material was removed through filtration. The filtrate was evaporated to dryness under reduced pressure, and the residue was purified through silica gel column chromatography (silica gel: 4 kg, eluent; hexane:ethyl acetate=3:1), to thereby yield the title compound as pale yellow syrup (3-position isomer mixtures) (925.2 g, 64%). The diastereomers in terms of the 3-position of pyrrolidine can be easily separable. However, since the subsequent step include reaction involving epimerization, the diastereomers were used without performing purification. 1H-NMR spectral data of each diastereomer, which had been separately isolated, are given below.

Provenance & Evidence