반응식
[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][CH:9]2[C:14](=O)[CH:13]3[CH2:16][CH2:17][N:10]2[CH2:11][CH2:12]3)[CH:5]=[N:6][CH:7]=1.NN.S(NN)(C1C=CC(C)=CC=1)(=O)=O.C([BH3-])#N.[Na+]>>[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][CH:9]2[CH2:14][CH:13]3[CH2:16][CH2:17][N:10]2[CH2:11][CH2:12]3)[CH:5]=[N:6][CH:7]=1참가 물질
실험 절차
The manner in which 2-((5-bromo-3-pyridyl)methyl)-1-azabicyclo[2.2.2]octane and other analogous compounds possessing substituents at the C-5 position of the pyridine ring are synthesized can vary. In another example, 2-((5-bromo-3-pyridyl)methyl)-1-azabicyclo[2.2.2]octane can be prepared starting with the aldol condensation of 5-bromo-3-pyridinecarboxaldehyde and 3-quinuclidinone hydrochloride (commercially available from Aldrich Chemical Company) which proceeds in 75% yield using potassium hydroxide in methanol. The carbon-carbon double bond of the resulting 2-((5-bromo-3-pyridyl)methylene)-1-azabicyclo[2.2.2]octan-3-one can be selectively reduced with an appropriate reducing agent, such as lithium tri-sec-butylborohydride (L-Selectride®) or potassium tri-sec-butylborohydride (K-Selectride®) (available from Aldrich Chemical Company) in tetrahydrofuran at −78° C. using methodology described by J. M. Fortunato et al., J Org. Chem. 41 (12): 2194-2200 (1976) or with sodium borohydride modified with nickel(1) chloride hexahydrate in an ethanolic or aqueous solution to give 2-((5-bromo-3-pyridyl)methyl)-1-azabicyclo[2.2.2]octan-3-one. The latter ketone can be reduced under Wolff-Kishner conditions with hydrazine and base (or under modified Wolff-Kishner conditions with tosylhydrazine and sodium cyanoborohydride) to yield 2-((5-bromo-3-pyridyl)methyl)-1-azabicyclo[2.2.2]octane.
출처 및 근거
- ORD 기록
- ord-0ea844da76f74f2d83f570f5177c30cd
- 출처 데이터셋
- uspto-grants-2002_08
- 특허 번호
- US06432975B1
연결된 노트
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