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

HRID 2303411Notes

Reaction equation

HRID 2303411 reaction equation
N1C=CC=C(C=O)C=1.Cl.N12CCC(CC1)C(=O)C2.[OH-].[K+].[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]=[C:28]2[C:33](=[O:34])[CH:32]3[CH2:35][CH2:36][N:29]2[CH2:30][CH2:31]3)[CH:22]=1>CO.[Ni]>[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][CH:28]2[CH:33]([OH:34])[CH:32]3[CH2:31][CH2:30][N:29]2[CH2:36][CH2:35]3)[CH:22]=1

Participants

7

Reactant 4

HCID 103713-PyridinecarboxaldehydeHCID 14797Potassium HydroxideHCID 1020191-Azabicyclo(2.2.2)octan-3-one, hydrochloride (1:1)HCID 6118222-(Pyridin-3-ylmethylidene)-1-azabicyclo[2.2.2]octan-3-one

Product 1

HCID 102200582-(3-Pyridinylmethyl)-3-quinuclidinol

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent

Procedure

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.

Workup

  1. customReact

Sources & evidence

ORD record
ord-bc5e7607e7874f47a1697f32efaeb08e
Source dataset
uspto-grants-2002_08
Patent number
US06432975B1

Reaction notes

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