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

HRID 2303425Notes

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 in a hydrogenation vessel, then wet Raney nickel (5 grams) was added in one portion. Hydrogenation (50 psig) was carried out for 12 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-ol as a light yellow oil, which dissolved in ethanol/HCl give a white crystalline solid upon cooling (0.78 g 77%).

Workup

stirringthe mixture was stirred for an additional 20 hrs

Sources & evidence

ORD record: ord-c17d26f6b56b45989e19dd7df5a10672
Source dataset: uspto-grants-2002_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06432975B1

Reaction notes

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