Reaction #586093

Reaction equation

2-((3-pyridinyl)methylene)-1-azabicyclo[2.2.2]octan-3-ol

sodium hydride

methyl iodide

2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octan-3-ol

phenol

3-phenoxy-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octane

2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octan-3-ol

triphenylphosphine

→

3-methoxy-2-((3-pyridinyl)methylene)-1-azabicyclo[2.2.2]octane

Solvents

ether

Conditions

Workup

1. 1
   Otherresults

Procedure

The saturated alcohol intermediates, such as 2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octan-3-ol, can also serve as templates for compound libraries. For instance, ethers can be generated from these alcohols, for example, using either Mitsunobu or Williamson conditions. Thus, by way of example, when 2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octan-3-ol is reacted with phenol via Mitsunobu coupling with diethylazidocarboxylate and triphenylphosphine (Guthrie et al., J. Chem. Soc., Perkin Trans I 45: 2328 (1981)), 3-phenoxy-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octane results. Similarly, when 2-((3-pyridinyl)methylene)-1-azabicyclo[2.2.2]octan-3-ol is treated with sodium hydride and methyl iodide, the unsaturated ether, 3-methoxy-2-((3-pyridinyl)methylene)-1-azabicyclo[2.2.2]octane, is formed. This gives the saturated ether, 3-methoxy-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octane (predominantly cis), upon catalytic hydrogenation.

Source