Citric Acid → 1-Benzyl 3-ethyl 4-oxopyrrolidine-1,3-dicarboxylate

HRID 2230243Notes

Reaction equation

HRID 2230243 reaction equation
[C:1]([O:5][CH2:6][CH3:7])(=[O:4])[CH:2]=[CH2:3].C(O[C:11](=[O:24])[CH2:12][NH:13][C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])C.[H-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH2:17]([O:16][C:14]([N:13]1[CH2:3][CH:2]([C:1]([O:5][CH2:6][CH3:7])=[O:4])[C:11](=[O:24])[CH2:12]1)=[O:15])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 8821Ethyl AcrylateHCID 14366N-((Phenylmethoxy)carbonyl)glycine ethyl esterHCID 24758Sodium hydride

Product 1

HCID 150432781-Benzyl 3-ethyl 4-oxopyrrolidine-1,3-dicarboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl acrylate (65.01 ml, 600.0 mmol) was added to a toluene (1,200 ml) solution containing N-benzyloxycarbonylglycine ethyl ester (156.3 g, 600.0 mmol) and then, under ice-cooling, sodium hydride (60% oil; 26.40 g, 660.0 mmol) was added thereto. After 10 minutes of stirring at the same temperature, the ice bath was taken off, and the mixture was stirred at room temperature for 20 minutes and then at 50° C. for 3 hours. After completion of the reaction, and under ice-cooling, the reaction solution was adjusted to about pH 3 by adding 10% citric acid aqueous solution and mixed with ethyl acetate, and the mixture was shaken and then subjected to separation of layers. The organic layer was separated and washed with saturated brine, and the water layer was further extracted with ethyl acetate. The organic layers were dried over anhydrous sodium sulfate and then filtered, and the solvent was evaporated under a reduced pressure to obtain 196.7 g (600.0 mmol, quantitative) of the title compound.

Workup

  1. temperatureunder ice-cooling
  2. stirringthe mixture was stirred at room temperature for 20 minutes
  3. waitat 50° C. for 3 hours
  4. customAfter completion of the reaction
  5. temperatureunder ice-cooling
  6. stirringthe mixture was shaken
  7. customsubjected to separation of layers
  8. customThe organic layer was separated
  9. washwashed with saturated brine
  10. extractionthe water layer was further extracted with ethyl acetate
  11. dry with materialThe organic layers were dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. customthe solvent was evaporated under a reduced pressure

Sources & evidence

ORD record
ord-181fde3ae9524a6095c42a2a2df0800b
Source dataset
uspto-grants-2002_07
Patent number
US06423843B1

Reaction notes

Loading…