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

Participants

Reaction Steps

The manner in which 3-(phenyloxy)-2-(3-pyridylmethyl)-1-azabicyclo[2.2.2]octane of the present invention is 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: 14-38 (1968). This aldol condensation product, 2-(3-pyridylmethylene)-1-azabicyclo[2.2.2]octan-3-one, 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. This alcohol is then etherified with phenol via Mitsunobu coupling with diethylazidocarboxylate and triphenylphosphine, as described by Guthrie et al., J. Chem. Soc., Perkin Trans I45: 2328 (1981), to afford the desired product, 3-(phenyloxy)-2-(3-pyridylmethyl)-1-azabicyclo[2.2.2]octane.

Provenance & Evidence