2,3,4,9-tetrahydro-1H-carbazol-1-one → 2,3,4,9-tetrahydro-1H-carbazol-1-amine

HRID 28675

Reaktionsgleichung

Reaktionsgleichung von HRID 28675
[C:1]1(=O)[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH2:4][CH2:3][CH2:2]1.Cl.[NH2:16]O.C([O-])(=O)C.[Na+]>C(O)C.O>[CH:1]1([NH2:16])[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH2:4][CH2:3][CH2:2]1

Komponenten

6

Edukt 3

HCID 2858652,3,4,9-tetrahydro-1H-carbazol-1-oneHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium Acetate

Produkt 1

HCID 100126712,3,4,9-tetrahydro-1H-carbazol-1-amine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel2×

Versuchsvorschrift

To a solution of 2,3,4,9-tetrahydro-1H-carbazol-1-one (1.5 g, 8.10 mmol) in ethanol (20 mL) was added a solution of hydroxylamine hydrochloride (1.13 g, 16.2 mmol) in water (10 mL) and a solution of sodium acetate (2.19 g, 26.7 mmol) in water (10 mL). The reaction mixture was heated at reflux for 2 h, cooled, and concentrated. The residue was diluted with water and extracted with ethyl acetate (2×100 mL). The organic phase was dried over sodium sulfate, filtered, and concentrated to a brown solid. The oxime was dissolved in THF (80 mL) and lithium aluminum hydride (1.0 M in THF, 24.3 mL) was added dropwise. The reaction was heated at reflux for 7 h and cooled in an ice bath. Methanol was added dropwise until bubbling ceased. The mixture was diluted with aqueous Na/K tartrate, stirred vigorously for 15 min and extracted with ethyl acetate (2×100 mL). The extracts were combined, dried over sodium sulfate, filtered and concentrated. The crude amine was purified by flash chromatography on silica (2% to 5% methanol/methylene chloride gradient) to provide 2,3,4,9-tetrahydro-1H-carbazol-1-amine as a brown oil. The oil was diluted in diethyl ether and HCl (1.0 M in diethyl ether) was added. The resulting precipitate was collected by filtration to provide 2,3,4,9-tetrahydro-1H-carbazol-1-amine hydrochloride (760 mg, 42%) as a light brown solid. 1H-NMR (CD3OD): δ 7.54 (d, 1H), 7.42 (d, 1H), 7.22 (t, 1H), 7.09 (t, 1H), 4.66 (t, 1H), 2.95-2.73 (m, 2H), 2.39-2.28 (m, 1H), 2.18-2.03 (m, 3H); MS m/z (M+1) 170.

Aufarbeitung

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 2 h
  3. temperaturecooled
  4. concentrationconcentrated
  5. additionThe residue was diluted with water
  6. extractionextracted with ethyl acetate (2×100 mL)
  7. dry with materialThe organic phase was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to a brown solid
  10. dissolutionThe oxime was dissolved in THF (80 mL)
  11. additionlithium aluminum hydride (1.0 M in THF, 24.3 mL) was added dropwise
  12. temperatureThe reaction was heated
  13. temperatureat reflux for 7 h
  14. temperaturecooled in an ice bath
  15. additionMethanol was added dropwise
  16. customuntil bubbling
  17. additionThe mixture was diluted with aqueous Na/K tartrate
  18. extractionextracted with ethyl acetate (2×100 mL)
  19. dry with materialdried over sodium sulfate
  20. filtrationfiltered
  21. concentrationconcentrated
  22. customThe crude amine was purified by flash chromatography on silica (2% to 5% methanol/methylene chloride gradient)

Quellen und Nachweise

ORD-Eintrag
ord-cf7cfe01e7c1482c9b4324da5bc365d6
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07419997B2

Verknüpfte Notizen

Wird geladen…