2-[(3-Nitrophenyl)methylidene]-1-azabicyclo[2.2.2]octan-3-one → 2-[(3-Nitrophenyl)methylene]-1-azabicyclo[2.2.2]octan-3-ol

HRID 2303405Notes

Reaction equation

HRID 2303405 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]2[C:16](=[O:17])[CH:15]3[CH2:18][CH2:19][N:12]2[CH2:13][CH2:14]3)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[BH4-].[Na+]>CO>[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[C:11]2[CH:16]([OH:17])[CH:15]3[CH2:18][CH2:19][N:12]2[CH2:13][CH2:14]3)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2]

Participants

4

Reactant 2

HCID 28566672-[(3-Nitrophenyl)methylidene]-1-azabicyclo[2.2.2]octan-3-oneHCID 4311764Sodium borohydride

Product 1

HCID 699696182-[(3-Nitrophenyl)methylene]-1-azabicyclo[2.2.2]octan-3-ol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The manner in which 2-[(3-aminophenyl)methyl]-1-azabicyclo[2.2.2]octane is synthesized can vary. For example, in one method, 3-nitrobenzaldehyde can be condensed with 3-quinuclidinone in an aldol reaction using potassium hydroxide and ethanol to yield 2-[(3-nitrophenyl)methylene]-1-azabicyclo[2.2.2]octan-3-one. The latter compound can be converted to the corresponding dithioketal by treatment with 1,2-ethanedithiol and boron triflouride etherate. Reduction and desulfurization can be effected by hydrogenation using Raney nickel to yield 2-[(3-aminophenyl)methyl]-1-azabicyclo[2.2.2]octane. Alternatively, in another method, the aldol product, 2-[(3-nitrophenyl)methylene]-1-azabicyclo[2.2.2]octan-3-one can be reduced by treatment with sodium borohydride in methanol to give the alcohol, 2-[(3-nitrophenyl)methylene]-1-azabicyclo[2.2.2]octan-3-ol. The latter compound can be converted to the chloro intermediate, 3-chloro-2-[(3-nitrophenyl)methylene]-1-azabicyclo[2.2.2]octane dihydrochloride upon treatment with thionyl chloride. Dechlorination by hydrogenation with Raney nickel and carbon-carbon double bond reduction by hydrogenation over 10% palladium on carbon can then be effected to yield 2-[(3-aminophenyl)methyl]-1-azabicyclo[2.2.2]octane. Replacement of 3-nitrobenzaldehyde with 2-nitrobenzaldehyde or 4-nitrobenzaldehyde in the above synthetic approach affords the isomeric compounds, 2-[(2-aminophenyl)methyl]-1-azabicyclo[2.2.2]octane and 2-[(4-aminophenyl)methyl]-1-azabicyclo[2.2.2]octane, respectively.

Sources & evidence

ORD record
ord-17e6e626fcc2493a84a5f378843f8da2
Source dataset
uspto-grants-2002_08
Patent number
US06432975B1

Reaction notes

Loading…