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

Participants

Reaction Steps

To a dichloromethane suspension (10 L) of 5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid (1165 g, 4.994 mol) was added o-tert-butyl-N,N′-diisopropylurea (3020 g, 15.00 mol) at room temperature with being stirred with a blade. After increase of inner temperature and beginning of reflux were observed, the solution was cooled in an ice water bath. The reaction solution was cooled to room temperature, subsequently the ice water bath was removed and the solution was stirred for an hour, and then with heating the solution up to 40° C. for 3 hours. After that, this reaction solution was cooled in an ice water bath and stirred for an hour. Subsequently, an insoluble material was removed by filtration, and the filtrate was dried under reduced pressure. Thus obtained residue was purified with silica gel column chromatography (silica gel: 4 kg; eluant: hexane/ethyl acetate in the ratio of 3:1) to obtain 925.2 g (64%) of the title compound (mixture with 3-position isomer) as a light yellow syrup. Each diastereomer derived from 3-position of pyrrolidine was able to be fractionated easily; however, the compound was used without fractionating the diastereomers because the subsequent step is a reaction involving epimerization.

Provenance & Evidence