3-Pyridinecarboxaldehyde → 2-(3-Pyridinylmethyl)-3-quinuclidinol

Participants

Reaction Steps

The manner in which 3-(phenylmethoxy and 2-phenylethoxy)-2-(3-pyridylmethyl)-1-azabicyclo[2.2.2]octanes of the present invention are synthesized can vary. For example, pyridine-3-carboxaldehyde and quinuclidin-3-one hydrochloride (commercially available from Aldrich) are reacted together in the presence of methanolic potassium hydroxide as described in Neilsen and Houlihan, Org. React. 16: 1-438 (1968). This aldol condensation product, 2-(3-pyridylmethylene)-1-azabicyclo[2.2.2]octan-3one, is then dissolved in methanol and hydrogenated in the presence of Raney nickel catalyst to afford 2-(3-pyridylmethyl)-1-azabicyclo[2.2.2]octan-3-ol. Treatment of the alcohol with sodium hydride followed by benzyl bromide in a suitable solvent affords the desired product, 3-(phenylmethoxy)-2-(3-pyridylmethyl)-azabicyclo[2.2.2]octane. 3-(2-Phenylethoxy)2-(3-pyridylmethyl)-1-azabicyclo[2.2.2]octane can be synthesized by substituting benzyl bromide with 2-bromoethylbenzene.

Provenance & Evidence