1,1'-Carbonyldiimidazole → 1H-Indole-3-carboxylic acid 1-azabicyclo[3.3.1]non-5-ylmethyl ester

HRID 1612750Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1612750
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([OH:12])=[O:11])=[CH:2]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[N:25]12[CH2:33][C:29]([CH2:34]O)([CH2:30][CH2:31][CH2:32]1)[CH2:28][CH2:27][CH2:26]2.C([Li])CCC.CCCCCC>O1CCCC1>[N:25]12[CH2:33][C:29]([CH2:34][O:11][C:10]([C:3]3[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[NH:1][CH:2]=3)=[O:12])([CH2:30][CH2:31][CH2:32]1)[CH2:28][CH2:27][CH2:26]2

Komponenten

6

Edukt 4

HCID 682631,1'-CarbonyldiimidazoleHCID 69867Indole-3-Carboxylic AcidHCID 19795980{1-Azabicyclo[3.3.1]nonan-5-yl}methanolHCID 178418244HCID 178418244, Verbindung

Produkt 1

HCID 541492491H-Indole-3-carboxylic acid 1-azabicyclo[3.3.1]non-5-ylmethyl esterAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

A solution of indole-3-carboxylic acid (1.62 g, 10 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (1.70 g, 10.5 mmol),stirred for one hour, and degassed with a stream of nitrogen for 10 minutes giving a suspension. Meanwhile, a cooled (-10° C.) solution of 1-azabicyclo[3.3.1]nonane-5-methanol (1.71 g, 11 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated (via syringe) with 2.5 N n-butyllithium/hexane (10.7 mmol), stirred for 30 minutes, concentrated in vacuo, and taken up in anhydrous tetrahydrofuran (10 mL) under nitrogen. The 1,1'-carbonyldiimidazole adduct suspension was transferred into this solution, and the mixture was stirred overnight (18 hours) and concentrated m vacuo. The residue was partitioned between methylene chloride (100 mL) containing a little isopropanol and saturated sodium carbonate (50 mL), and the organic layer was separated. The aqueous solution was dried (Na2SO4), concentrated in vacuo, and filtered through alumina (eluted with 7% methanol/methylene chloride). The filtrated was concentrated in vacuo and the residue was triturated from cold ether and recrystallized from acetonitrile (2 crops) to afford 1.79 g (60% ) of colorless crystals; m.p. 207°-209° C.

Aufarbeitung

  1. customdegassed with a stream of nitrogen for 10 minutes
  2. customgiving a suspension
  3. concentrationconcentrated in vacuo
  4. stirringthe mixture was stirred overnight (18 hours)
  5. concentrationconcentrated m vacuo
  6. customThe residue was partitioned between methylene chloride (100 mL)
  7. additioncontaining a little isopropanol and saturated sodium carbonate (50 mL)
  8. customthe organic layer was separated
  9. dry with materialThe aqueous solution was dried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. filtrationfiltered through alumina (eluted with 7% methanol/methylene chloride)
  12. concentrationThe filtrated was concentrated in vacuo
  13. customthe residue was triturated from cold ether
  14. customrecrystallized from acetonitrile (2 crops)

Quellen und Nachweise

ORD-Eintrag
ord-bece60835dbc43cca98ca1d091b2a97f
Quelldatensatz
uspto-grants-1993_03
Patentnummer
US05190953

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