Phenol → 3-Methoxy-2-((3-pyridinyl)methylene)-1-azabicyclo[2.2.2]octane

HRID 44661Notes

Reaction equation

HRID 44661 reaction equation
N1C=CC=C(CC2C(O)C3CCN2CC3)C=1.C1(O)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O:43]([CH:50]1[CH:55]2[CH2:56][CH2:57][N:52]([CH2:53][CH2:54]2)[CH:51]1[CH2:58][C:59]1[CH:60]=[N:61][CH:62]=[CH:63][CH:64]=1)[C:44]1C=CC=CC=1.N1C=CC=C(C=C2C(O)C3CCN2CC3)C=1.[H-].[Na+].CI>CCOCC>[CH3:44][O:43][CH:50]1[CH:55]2[CH2:56][CH2:57][N:52]([CH2:53][CH2:54]2)[C:51]1=[CH:58][C:59]1[CH:60]=[N:61][CH:62]=[CH:63][CH:64]=1

Participants

9

Reactant 7

HCID 996PhenolHCID 6328Methyl iodideHCID 11776TriphenylphosphineHCID 24758Sodium hydrideHCID 6122812-((3-Pyridyl)methylene)-1-azabicyclo[2.2.2]octan-3-olHCID 102200582-(3-Pyridinylmethyl)-3-quinuclidinol2×HCID 223113593-(Phenyloxy)-2-(3-pyridylmethyl)-1-azabicyclo[2.2.2]octane

Product 1

HCID 667731293-Methoxy-2-((3-pyridinyl)methylene)-1-azabicyclo[2.2.2]octane

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

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 145: 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.

Workup

  1. customresults

Sources & evidence

ORD record
ord-5f73ea21e8c84d30b1a772b48ff377fd
Source dataset
uspto-grants-2013_09
Patent number
US08541447B2

Reaction notes

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