반응 #2390595

ord-728ef7d744a245bfb7284c2bdf24fcf9

반응 방정식

[BH4-].[Na+]
sodium borohydride
Brc1cncc(CC2CC3CCN2CC3)c1
2-((5-bromo-3-pyridyl)methyl)-1-azabicyclo[2.2.2]octane
[K+].[OH-]
potassium hydroxide
[C].[C]
carbon carbon
O=C1C(=Cc2cncc(Br)c2)N2CCC1CC2
2-((5-bromo-3-pyridyl)methylene)-1-azabicyclo[2.2.2]octan-3-one
CCC(C)[BH-](C(C)CC)C(C)CC.[K+]
potassium tri-sec-butylborohydride
Brc1cncc(CC2CC3CCN2CC3)c1
2-((5-bromo-3-pyridyl)methyl)-1-azabicyclo[2.2.2]octane
CCC(C)[BH-](C(C)CC)C(C)CC.[Li+]
lithium tri-sec-butylborohydride
O=Cc1cncc(Br)c1
5-bromo-3-pyridinecarboxaldehyde
Cl.O=C1CN2CCC1CC2
3-quinuclidinone hydrochloride
O=C1C2CCN(CC2)C1Cc1cncc(Br)c1
2-((5-bromo-3-pyridyl)methyl)-1-azabicyclo[2.2.2]octan-3-one
수율 75.0%

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타are synthesized can
  2. 2
    기타at −78° C.

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

DOI: 10.6084/m9.figshare.5104873.v1특허: US06432975B1uspto-grants-2002_08