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

HRID 2303419Notes

Reaction equation

Cl.[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C:4](=[O:10])[CH2:3]2.[OH-].[K+].[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]=O)[CH:14]=1>CO.O>[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]=[C:3]2[C:4](=[O:10])[CH:5]3[CH2:8][CH2:9][N:2]2[CH2:7][CH2:6]3)[CH:14]=1

Participants

Conditions

Temperature: 0 °C

Procedure

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%).

Workup

stirringthe mixture was stirred for an additional 20 hrs

Sources & evidence

ORD record: ord-1189692ff39f4ee7b6757244cdd0428d
Source dataset: uspto-grants-2002_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06432975B1

Reaction notes

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