Potassium Hydroxide → 6-Methyl-3-(3-phenylpropyl)-6-(3-pyridinyl)-3-azabicyclo[3.1.0]hexane-2,4-dione

HRID 1826465Notes

Reaction equation

HRID 1826465 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7](=NN)[CH3:8])[CH:2]=1.[OH-].[K+].[C:13]1([CH2:19][CH2:20][CH2:21][N:22]2[C:26](=[O:27])[CH:25]=[CH:24][C:23]2=[O:28])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>O1CCOCC1.C(O)C.[O-2].[O-2].[Mn+4]>[NH3:1].[CH3:8][C:7]1([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH:25]2[CH:24]1[C:23](=[O:28])[N:22]([CH2:21][CH2:20][CH2:19][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[C:26]2=[O:27]

Participants

8

Reactant 3

HCID 14797Potassium HydroxideHCID 576189N-(3-Phenylpropyl)maleimideHCID 598980421-(3-Pyridinyl)-1-ethanone hydrazone

Product 2

HCID 222AmmoniaHCID 221413206-Methyl-3-(3-phenylpropyl)-6-(3-pyridinyl)-3-azabicyclo[3.1.0]hexane-2,4-dioneYield 28%

Reagents, catalysts & solvents 3

HCID 178418406HCID 178418406, compoundCatalystHCID 702EthanolSolventHCID 312751,4-DioxaneSolvent

Procedure

1-(3-Pyridinyl)-1-ethanone hydrazone (Preparation 76, 0.69 g, 5.3 mmol) was dissolved in dioxan (30 ml) and manganese dioxide (0.85 g, 5.3 mmol) was added portionwise followed by a saturated solution of potassium hydroxide in ethanol (0.5 ml). The reaction mixture was stirred at room temperature for 1.5 h and then filtered through a pad of Celite®. To half of the filtrate was added 1-(3-phenylpropyl)-1H-pyrrole-2,5-dione (Preparation 80, 0.57 g, 2.6 mmol) and the reaction mixture was heated to 90° C. for 7 h and then cooled to room temperature for 16 h. The reaction mixture was heated under reflux for 16 h and then cooled to room temperature for 72 h before concentrating in vacuo. The reaction mixture was purified by chromatography using silica gel (30 g) eluting with dichloromethane:0.880 ammonia (99:1) and then dichloromethane:methanol:0.880 ammonia (97:2:1) to afford the title compound as an oil (230 mg, 28%).

Workup

  1. filtrationfiltered through a pad of Celite®
  2. temperaturethe reaction mixture was heated to 90° C. for 7 h
  3. temperaturecooled to room temperature for 16 h
  4. temperatureThe reaction mixture was heated
  5. temperatureunder reflux for 16 h
  6. temperaturecooled to room temperature for 72 h
  7. concentrationbefore concentrating in vacuo
  8. customThe reaction mixture was purified by chromatography
  9. washeluting with dichloromethane

Sources & evidence

ORD record
ord-567a7f7b76bb41dc94d1dbd591a8acce
Source dataset
uspto-grants-2006_05
Patent number
US07049444B2

Reaction notes

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