Dimethyl Sulfoxide → (3S)-3-(3-Oxo-1-propyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester

HRID 1917403Notes

Reaction equation

HRID 1917403 reaction equation
C(=O)=O.CO.C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:16]([O:20][C:21]([C@@:23]1([CH2:37][CH2:38][CH2:39][OH:40])[CH2:27][C:26](=[O:28])[N:25]([C@@H:29]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH3:30])[CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].C(N(CC)CC)C.[Cl-].[NH4+]>ClCCl>[C:16]([O:20][C:21]([C@@:23]1([CH2:37][CH2:38][CH:39]=[O:40])[CH2:27][C:26](=[O:28])[N:25]([C@@H:29]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH3:30])[CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]

Participants

8

Reactant 6

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 65578Oxalyl chlorideHCID 21973728Carbon dioxide methanolHCID 67491012(3S)-3-(3-hydroxy-1-propyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 86664654(3S)-3-(3-Oxo-1-propyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl esterYield 100.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Dichloromethane (35 ml) was cooled with dry ice-methanol in a nitrogen atmosphere. Oxalyl chloride (3.45 ml, 39.5 mmol) and dimethyl sulfoxide (4.68 ml, 66.0 mmol) were added, and the mixture was stirred under cooling for 15 minutes. A solution of (3S)-3-(3-hydroxy-1-propyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (4.58 g, 13.2 mmol) in dichloromethane (31 mL) was added, and the mixture was stirred under cooling for one hour. Triethylamine (11.1 ml, 79.5 mmol) was added under cooling, and the mixture was stirred under cooling for one hour and then at room temperature for one hour. A saturated ammonium chloride solution (100 ml) was added to the reaction solution, followed by extraction with chloroform (100 ml×1, 80 ml×1). The organic layer was washed with brine (120 ml) and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0→90:10→66:34→60:40→50:50→40:60→34:66→25:75) to give 4.59 g of the title compound as white crystals.

Workup

  1. temperatureunder cooling for 15 minutes
  2. stirringthe mixture was stirred
  3. temperatureunder cooling for one hour
  4. temperatureunder cooling
  5. stirringthe mixture was stirred
  6. temperatureunder cooling for one hour
  7. extractionfollowed by extraction with chloroform (100 ml×1, 80 ml×1)
  8. washThe organic layer was washed with brine (120 ml)
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationAfter filtration
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=100:0→90:10→66:34→60:40→50:50→40:60→34:66→25:75)

Sources & evidence

ORD record
ord-7cc9a4cf453d45d99927985d35ed6fbe
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

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