2-(Pyridin-3-ylmethylidene)-1-azabicyclo[2.2.2]octan-3-one → 2-(Pyridin-3-ylmethyl)quinuclidin-3-one

Participants

Reaction Steps

Quinuclidin-3-one hydrochloride (4.6 g, 28.3 mmol) and powdered anhydrous potassium hydroxide (2.1 g, 37.2 mmol) were dissolved in methanol (25 ml) and stirred for 15 mins. Pyridine-3-carboxaldehyde (3.2 g, 29.5 mmol) was then added in one portion and the mixture was stirred for an additional 20 hrs. The reaction mixture was then diluted with 40 ml water and cooled to 0° C. yielding 2-((3-pyridyl)methylene)-1-azabicyclo[2.2.2]octan-3-one as a yellow precipitate, which was collected, washed with distilled water and dried under vacuum (5.16 g, 81.4%). 2-((3-Pyridyl)methylene)-1-azabicyclo[2.2.2]octan-3-one (1.0 g, 4.7 mmol) was combined with 50 ml methanol and 0.2 g palladium on charcoal (5% w/w) in a hydrogenation vessel. Hydrogenation (50 psig) was carried out for 4 hrs., after which time the slurry was carefully filtered through a pad of Celite filter aid. Evaporation of solvent gave 2-((3-pyridyl)methyl)-1-azabicyclo[2.2.2]octan-3-one as white semisolid, which dissolved in ethanol give a white crystalline solid upon cooling (0.82 g 88%).

Provenance & Evidence