(3aRS,4RS,6aSR)-2-benzyl-4-(4-bromobenzyl)-5,6,6-trimethyl-tetrahydro-pyrrolo[3,4-c]pyrrole-1,3-dione → (1RS,3aSR,6aRS)-4-(5-benzyl-2,3,3-trimethyl-4,6-dioxo-octahydro-pyrrolo[3,4-c]pyrrol-1-ylmethyl)-benzonitrile

HRID 2293301Notes

Reaction equation

HRID 2293301 reaction equation
[CH2:1]([N:8]1[C:15](=[O:16])[CH:14]2[CH:10]([C:11]([CH3:27])([CH3:26])[N:12]([CH3:25])[CH:13]2[CH2:17][C:18]2[CH:23]=[CH:22][C:21](Br)=[CH:20][CH:19]=2)[C:9]1=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cu][C:30]#[N:31]>CN(C=O)C>[CH2:1]([N:8]1[C:9](=[O:28])[CH:10]2[C:11]([CH3:27])([CH3:26])[N:12]([CH3:25])[CH:13]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([C:30]#[N:31])=[CH:20][CH:19]=3)[CH:14]2[C:15]1=[O:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 69953772(3aRS,4RS,6aSR)-2-benzyl-4-(4-bromobenzyl)-5,6,6-trimethyl-tetrahydro-pyrrolo[3,4-c]pyrrole-1,3-dioneHCID 178418546HCID 178418546, compound

Product 1

HCID 69954349(1RS,3aSR,6aRS)-4-(5-benzyl-2,3,3-trimethyl-4,6-dioxo-octahydro-pyrrolo[3,4-c]pyrrol-1-ylmethyl)-benzonitrileYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3.45 g (7.82 mmol) of (3aRS,4RS,6aSR)-2-benzyl-4-(4-bromobenzyl)-5,6,6-trimethyl-tetrahydro-pyrrolo[3,4-c]pyrrole-1,3-dione and 3.52 g (39.1 mmol) of copper(I) cyanide were suspended in 150 ml of DMF under argon and heated under reflux for 56 hours. After cooling about 100 ml of DMF were removed, then 150 ml of dichloromethane and 60 ml of concentrated aqueous ammonia solution were added. The mixture was stirred vigorously for a few hours. The blue aqueous phase was separated and the organic phase was washed twice with ammonia solution and once with water. The solvent was removed and the residue was purified chromatographically (hexane/ethyl acetate 1:1+1% triethylamine). 1.91 g of (1RS,3aSR,6aRS)-4-(5-benzyl-2,3,3-trimethyl-4,6-dioxo-octahydro-pyrrolo[3,4-c]pyrrol-1-ylmethyl)-benzonitrile were isolated as a yellowish oil. FAB-MS: 775 ([2M+H]+, 1); 663 (2); 388 ([M+H]+, 58); 271 (100); 91 (42).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 56 hours
  3. customwere removed
  4. addition150 ml of dichloromethane and 60 ml of concentrated aqueous ammonia solution were added
  5. customThe blue aqueous phase was separated
  6. washthe organic phase was washed twice with ammonia solution and once with water
  7. customThe solvent was removed
  8. customthe residue was purified chromatographically (hexane/ethyl acetate 1:1+1% triethylamine)

Sources & evidence

ORD record
ord-af072824ef7446f68c4e4d1ab6f81f13
Source dataset
uspto-grants-1997_11
Patent number
US05686459

Reaction notes

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