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

HRID 1675196Notes

Reaction equation

HRID 1675196 reaction equation
[O:1]=[C:2]1[N:6]([C@@H:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH3:8])[CH2:5][CH:4]([C:15]([OH:17])=[O:16])[CH2:3]1>ClCCl>[O:1]=[C:2]1[N:6]([C@@H:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH3:8])[CH2:5][CH:4]([C:15]([O:17][C:4]([CH3:15])([CH3:5])[CH3:3])=[O:16])[CH2:3]1

Participants

3

Reactant 1

HCID 134225555-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid

Product 1

HCID 57758674HCID 57758674, compoundYield 128%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  1. temperatureAfter increase of inner temperature and beginning
  2. temperatureof reflux
  3. temperaturethe solution was cooled in an ice water bath
  4. customsubsequently the ice water bath was removed
  5. stirringthe solution was stirred for an hour
  6. temperaturewith heating the solution up to 40° C. for 3 hours
  7. temperatureAfter that, this reaction solution was cooled in an ice water bath
  8. stirringstirred for an hour
  9. customSubsequently, an insoluble material was removed by filtration
  10. customthe filtrate was dried under reduced pressure
  11. customThus obtained residue was purified with silica gel column chromatography (silica gel

Sources & evidence

ORD record
ord-609fce24243044b6ad5ab7c90078cf36
Source dataset
uspto-grants-2011_08
Patent number
US08003666B2

Reaction notes

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