Ethanol → 1,4-Bis(ethoxycarbonyl)-2-(diphenylmethyl)-pyrrolidin-3-one

HRID 2210683Notes

Reaction equation

HRID 2210683 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6]([NH:8][CH:9]([CH:14]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:10](OC)=[O:11])=[O:7])[CH3:4].C(O)C.[C:30]([O:34][CH2:35][CH3:36])(=[O:33])[CH:31]=[CH2:32]>C1C=CC=CC=1>[CH2:3]([O:5][C:6]([N:8]1[CH2:32][CH:31]([C:30]([O:34][CH2:35][CH3:36])=[O:33])[C:10](=[O:11])[CH:9]1[CH:14]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:7])[CH3:4]

Participants

6

Reactant 4

HCID 702EthanolHCID 8821Ethyl AcrylateHCID 24758Sodium hydrideHCID 19379388Methyl 2-ethoxycarbonylamino-3,3-diphenylpropanoate

Product 1

HCID 193794111,4-Bis(ethoxycarbonyl)-2-(diphenylmethyl)-pyrrolidin-3-one

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent2×

Procedure

To a suspension of 80% sodium hydride (2.48 g, 83 mmol) in benzene (50 ml) was slowly added a solution of methyl 2- ethoxycarbonylamino- 3,3-diphenylpropanoate (Example 1b, 27.0 g, 83 mmol) in benzene (200 ml) and the mixture then heated at reflux for 1 h. Ethanol (1.0 ml) followed by ethyl acrylate (8.95 ml, 83 mmol) were added and the reaction heated at reflux for 2 h, the solvent was then distilled off and the residue allowed to cool to room temperature. A solution of the residue in water was added to a concentrated sulphuric acid/ice mixture and the product extracted into ethyl acetate. The organic phase was washed with saturated brine and dried (MgSO4). The residue was chromatographed on silica gel in dichloromethane/methanol (97:3) to give 1,4-bis(ethoxycarbonyl)-2-(diphenylmethyl)-pyrrolidin-3-one, m/z (CI+) 396(MH). A solution of this oil in 1.0M oxalic acid was heated at reflux for 8 h, cooled and the product extracted into chloroform. After separation the chloroform was removed in vacuo and the residue chromatographed on silica gel using ethyl acetate/hexane (1:4) as eluant to give 2-(diphenylmethyl)-1-ethoxycarbonylpyrrolidin-3 -one. 1H NMR (250 MHz, CDCl3) δ7.14-7.52 (10H, m), 4.80 (1H, br s), 4.68 (1H, vbr s), 4.18 (2H, br q), 3.94 (1H, vbs), 3.06 (1H, m), 2.34 (1H, m), 1.76 (1H, m), 1.22 (3H, t, J=7.0 Hz). m/z (CI+) 324(MH).

Workup

  1. temperaturethe mixture then heated
  2. temperatureat reflux for 1 h
  3. additionwere added
  4. temperaturethe reaction heated
  5. temperatureat reflux for 2 h
  6. distillationthe solvent was then distilled off
  7. additionA solution of the residue in water was added to a concentrated sulphuric acid/ice mixture
  8. extractionthe product extracted into ethyl acetate
  9. washThe organic phase was washed with saturated brine
  10. dry with materialdried (MgSO4)
  11. customThe residue was chromatographed on silica gel in dichloromethane/methanol (97:3)

Sources & evidence

ORD record
ord-a7e2613ca9084bbbabdcbf12260eea40
Source dataset
uspto-grants-1995_10
Patent number
US05459270

Reaction notes

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