psi-Pelletierine → (E)-5-(2-(8-azabicyclo[3.2.1]oct-6-yl)ethenyl)isoxazole

HRID 1168212

Reaktionsgleichung

Reaktionsgleichung von HRID 1168212
C[N:2]1[CH:7]2[CH2:8][C:9]([CH2:11][CH:3]1[CH2:4][CH2:5][CH2:6]2)=O.C[N:13]1C2[CH2:18][C:19]([CH2:21][CH:14]1CC2)=[O:20].[H-].C([Al+]CC(C)C)C(C)C.[O:32]1[C:36]([CH2:37]P(=O)(OCC)OCC)=[CH:35][CH:34]=[N:33]1>>[CH:3]12[NH:2][CH:7]([CH:5](/[CH:6]=[CH:18]/[C:19]3[O:20][N:13]=[CH:14][CH:21]=3)[CH2:4]1)[CH2:8][CH2:9][CH2:11]2.[CH:3]12[NH:2][CH:7]([CH:5](/[CH:6]=[CH:37]\[C:36]3[O:32][N:33]=[CH:34][CH:35]=3)[CH2:4]1)[CH2:8][CH2:9][CH2:11]2

Komponenten

6

Edukt 4

HCID 11096psi-Pelletierine2×HCID 79038Npc164516HCID 11378989Diethyl(5-isoxazolylmethyl)phosphonateHCID 21225700Diisobutylaluminumhydride

Produkt 2

HCID 9855792(E)-5-(2-(8-azabicyclo[3.2.1]oct-6-yl)ethenyl)isoxazoleHCID 69588569(Z)-5-(2-(8-azabicyclo[3.2.1]oct-6-yl)ethenyl)isoxazole

Versuchsvorschrift

The synthesis of arylethenyl-substituted 8-azabicyclo[3.2.1]octanes and arylethynyl-substituted 8-azabicyclo[3.2.1]octanes are accomplished in a manner similar to that described for arylethenyl-substituted 7-azabicyclo[2.2.1]heptanes and arylethynyl-substituted 7-azabicyclo[2.2.1]heptanes. Treatment of pseudopelletierine (N-methyl-9-azabicyclo[3.3.1]nonan-3-one) as described earlier for tropinone (Daly et al. Eur. J. Pharmacol. 321:189-194 (1997)) will generate ethyl 8-aza-6-(ethoxycarbonyl)bicyclo[3.2.1]octane-8-carboxylate. Pseudopelletierine is made according to Howell et al., Org. Syn. Coll. Vol IV: 816-819 (1963). Reduction of ethyl 8-aza-6-(ethoxycarbonyl)bicyclo[3.2.1]octane-8-carboxylate with diisobutylaluminum hydride and subsequent reaction of the 6-formyl derivative with diethyl (5-isoxazolylmethyl)phosphonate and n-butylithium will provide mixture of ethyl (E)- and (Z)-5-(2-(8-azabicyclo[3.2.1]oct-6-yl)ethenyl)isoxazole-8-carboxylate. Separation of the isomers followed by deprotection will provide (E)-5-(2-(8-azabicyclo[3.2.1]oct-6-yl)ethenyl)isoxazole and (Z)-5-(2-(8-azabicyclo[3.2.1]oct-6-yl)ethenyl)isoxazole. The other methods described previously for the preparation of five-membered heterocycle analogues of ethenyl-substituted 7-azabicyclo[2.2.1]heptanes may be applied similarly.

Aufarbeitung

  1. customwill provide
  2. customSeparation of the isomers

Quellen und Nachweise

ORD-Eintrag
ord-0129d242b1d74a1185d4b8d147c7113c
Quelldatensatz
uspto-grants-2003_09
Patentnummer
US06624167B1

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