Benzaldehyde → 2-Benzylidene-3-quinuclidinone

HRID 984790Notes

Reaction equation

HRID 984790 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C:3](=[O:9])[CH2:2]2.[CH:10](=O)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[OH-].[K+].O>CO>[CH:10](=[C:2]1[C:3](=[O:9])[CH:4]2[CH2:7][CH2:8][N:1]1[CH2:6][CH2:5]2)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 962WaterHCID 14797Potassium HydroxideHCID 195073-Quinuclidinone

Product 1

HCID 2433762-Benzylidene-3-quinuclidinoneYield 62%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 3-quinuclidinone (6.25 g, 50 mmol), benzaldehyde (5.83 g, 55 mmol) and KOH (0.84 g, 15 mmol) in 30 mL MeOH is heated under reflux for 16 h. The reaction is cooled and water is added. The mixture is extracted with CHCl3, dried (MgSO4), filtered and concentrated. The yellow solid is triturated with warm heptane, filtered and dried to provide 6.6 g (62%) of 2-benzylidene-1-azabicyclo[2.2.2]octan-3-one. A suspension of 2-benzylidene-1-azabicyclo[2.2.2]octan-3-one (6.6 g, 31 mmol) in MeOH is treated with a THF slurry of 10% Pd/C (0.38 g) in a Parr hydrogenation bottle. The bottle is charged with 40 psi of hydrogen gas and allowed to shake for 1 h. The mixture is filtered through Celite, and the solvent is removed in vacuo. The residue is purified by chromatography (Biotage 40M, 30% EtOAc/hexanes—100% EtOAc) to afford 0.48 g (7%) of 2-benzylidene-1-azabicyclo[2.2.2]octan-3-ol and 4.8 g (72%) of 2-benzylquinuclidin-3-one. MS (ESI+) for C14H17NO m/z 216.1 (M+H)+.

Workup

  1. temperatureis heated
  2. temperatureunder reflux for 16 h
  3. temperatureThe reaction is cooled
  4. extractionThe mixture is extracted with CHCl3
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe yellow solid is triturated with warm heptane
  9. filtrationfiltered
  10. customdried

Sources & evidence

ORD record
ord-463d9a4da7b44191981eacc8f44fbb44
Source dataset
uspto-grants-2005_03
Patent number
US06869946B2

Reaction notes

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