Ethyl 2-(2-nitroethyl)-1-benzylpyrrolidine-2-carboxylate → 1-Benzyl-1,7-diazaspiro[4.4]nonan-6-one

HRID 967919Notes

Reaction equation

HRID 967919 reaction equation
[N+:1]([CH2:4][CH2:5][C:6]1([C:18]([O:20]CC)=O)[CH2:10][CH2:9][CH2:8][N:7]1[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([O-])=O>[Ni].C(O)C>[CH2:11]([N:7]1[CH2:8][CH2:9][CH2:10][C:6]21[C:18](=[O:20])[NH:1][CH2:4][CH2:5]2)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

4

Reactant 1

HCID 22291241Ethyl 2-(2-nitroethyl)-1-benzylpyrrolidine-2-carboxylate

Product 1

HCID 222912221-Benzyl-1,7-diazaspiro[4.4]nonan-6-oneYield 93.1%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 702EthanolSolvent

Procedure

Raney nickel (˜2 g) was added to a solution of ethyl 2-(2-nitroethyl)-1-benzylpyrrolidine-2-carboxylate (6.00 g, 19.6 mmol) in absolute ethanol (200 mL) in a hydrogenation bottle. The mixture was shaken for 12 h under a hydrogen atmosphere (50 psi) in a Parr hydrogenation apparatus, filtered through a Celite pad and concentrated by rotary evaporation. GCMS analysis indicated that the hydrogenation product was a mixture of the primary amine and the lactam resulting from cyclization of the amine onto the ester. The mixture was dissolved in toluene (150 mL). A catalytic amount of p-toluenesulfonic acid (˜30 mg) was added and the mixture was heated at reflux under a nitrogen atmosphere for 24 h. Upon evaporation of the toluene, the residue (now entirely lactam, by GCMS) crystallized to give 4.20 g (93.1%) of tan solid (mp 152-153° C.).

Workup

  1. filtrationfiltered through a Celite pad
  2. concentrationconcentrated by rotary evaporation
  3. additiona mixture of the primary amine
  4. dissolutionThe mixture was dissolved in toluene (150 mL)
  5. additionA catalytic amount of p-toluenesulfonic acid (˜30 mg) was added
  6. temperaturethe mixture was heated
  7. temperatureat reflux under a nitrogen atmosphere for 24 h
  8. customUpon evaporation of the toluene
  9. customthe residue (now entirely lactam, by GCMS) crystallized

Sources & evidence

ORD record
ord-6765748dd20e41cd828950e475ad2d3b
Source dataset
uspto-grants-2005_10
Patent number
US06956042B2

Reaction notes

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