4-Nitrobenzaldehyde → HCID 69953773, compound

HRID 2293313Notes

Reaction equation

HRID 2293313 reaction equation
[NH:1]1[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3](O)=O.[N+:9]([C:12]1[CH:19]=[CH:18][C:15]([CH:16]=O)=[CH:14][CH:13]=1)([O-:11])=[O:10].[CH2:20]([N:24]1[C:28](=[O:29])C=[CH:26][C:25]1=[O:30])[CH2:21][CH2:22][CH3:23]>CN(C=O)C>[CH2:20]([N:24]1[C:25](=[O:30])[CH:26]2[CH:16]([C:15]3[CH:18]=[CH:19][C:12]([N+:9]([O-:11])=[O:10])=[CH:13][CH:14]=3)[N:1]3[CH:2]([CH:3]2[C:28]1=[O:29])[CH2:6][CH2:7][CH2:8]3)[CH2:21][CH2:22][CH3:23]

Participants

5

Reactant 3

HCID 5414-NitrobenzaldehydeHCID 145742L-ProlineHCID 2397801-Butyl-1H-pyrrole-2,5-dione

Product 1

HCID 69953773HCID 69953773, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of L-proline (20 mmol), 4-nitrobenzaldehyde (20 mmol) and N-butylmaleimide (20 mmol) was heated to 80° C. in DMF (20 ml) for 24 hours. The solvent was removed in a high vacuum and the residue was separated chromatographically over silica gel (eluent hexane:ethyl acetate=1:1+1% triethylamine). (3aRS, 4SR,8aRS,8bSR)-2-Butyl-4-(4-nitro-phenyl)-hexahydro-pyrrolo[3,4-a]pyrrolizine-1,3-dione was obtained in 32% yield as a yellow solid (Rf =0.35). This product in 50 ml of ethanol was treated with 200 mg of 10% palladium on charcoal and reduced under hydrogen within 8 hours. After filtration of the catalyst and removal of the solvent in a vacuum (3aRS,4SR,8aRS,8bSR)-4-(4-amino-phenyl)-2-butyl-hexahydro-pyrrolo[3,4-a]pyrrolizine-1,3-dione was obtained as a pale yellow oil (Rf =0.23). 120 mg of this crude product were treated with 80 mg of 3,5-dimethyl-pyrazolyl-1-carboximidamidinium nitrate in 20 ml of DMF and heated at 80° C. for 48 hours. After removing the solvent in a vacuum the material remaining was separated on a RP-18 chromatography column with a water/methanol gradient. (3aRS,4SR,8aRS, 8bSR)-N-[4-(2-Butyl-1,3-dioxo-decahydro-pyrrolo[3,4-a]pyrrolizin-4-yl)-phenyl]-guanidinium nitrate was obtained in 12% yield as a pale yellow oil. ISP-MS: 483.4 ([M+H]+, 100).

Workup

  1. customThe solvent was removed in a high vacuum
  2. customthe residue was separated chromatographically over silica gel (eluent hexane:ethyl acetate=1:1+1% triethylamine)

Sources & evidence

ORD record
ord-9560141df8044bda93c50755e0a1ef27
Source dataset
uspto-grants-1997_11
Patent number
US05686459

Reaction notes

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