Hydrochloric Acid → (4s,7r)-2-Phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

HRID 1437864Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1437864
[CH3:1][C@:2]12[C:8]([CH3:10])([CH3:9])[C@H:5]([CH2:6][CH2:7]1)[CH:4]([C:11](Cl)=[O:12])[C:3]2=O.C(=[N:17][NH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)C.N1C=CC=CC=1.Cl>ClCCCl.O1CCOCC1.C(O)(=O)C>[C:19]1([N:18]2[C:11](=[O:12])[C:4]3[C@@H:5]4[C:8]([CH3:10])([CH3:9])[C@@:2]([CH3:1])([CH2:7][CH2:6]4)[C:3]=3[NH:17]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 70285Acetaldehyde, 2-phenylhydrazoneHCID 57941306(1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride2×

Produkt 1

HCID 57941335(4s,7r)-2-Phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-oneAusbeute 97 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 111,2-DichloroethaneLösungsmittel2×HCID 176Acetic AcidLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A solution of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 4.36 g, 20.3 mmol) in 1,2-dichloroethane (40 mL) was added over a period of one minute to a cooled (˜0° C.) solution of N-ethylidene-N′-phenyl-hydrazine (prepared according to A. R. Maguire et al. Bioorg. Med. Chem. 2001, 9, 745-762; 2.60 g, 19.4 mmol) and pyridine (2.5 mL, 30.9 mmol) in 1,2-dichloroethane (20 mL). The reaction mixture was stirred at room temperature for 15 min and then at 50° C. for 25 min. It was then cooled to room temperature and 4M HCl in dioxane (12 mL) was added. The reaction mixture was stirred for 5 min at room temperature, then glacial acetic acid (20 mL) was added and the mixture was heated in an oil bath at 100° C. for 20 min. The reaction mixture was cooled to room temperature and then evaporated. Dichloromethane (200 mL) was added, the solution was washed with 50% saturated brine (2×50 mL), and the combined aqueous layers were back-extracted with dichloromethane (2×100 mL). The combined organic layers were washed with brine (150 mL), dried (magnesium sulfate), filtered, evaporated and eluted through a plug of silica gel with 30% ethyl acetate/hexanes to give (4S,7R)-2-phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (5.04 g, 97%) as an orange foam.

Aufarbeitung

  1. customprepared
  2. waitat 50° C. for 25 min
  3. temperatureIt was then cooled to room temperature
  4. stirringThe reaction mixture was stirred for 5 min at room temperature
  5. temperaturethe mixture was heated in an oil bath at 100° C. for 20 min
  6. temperatureThe reaction mixture was cooled to room temperature
  7. customevaporated
  8. additionDichloromethane (200 mL) was added
  9. washthe solution was washed with 50% saturated brine (2×50 mL)
  10. extractionthe combined aqueous layers were back-extracted with dichloromethane (2×100 mL)
  11. washThe combined organic layers were washed with brine (150 mL)
  12. dry with materialdried (magnesium sulfate)
  13. filtrationfiltered
  14. customevaporated
  15. washeluted through a plug of silica gel with 30% ethyl acetate/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-caa3fa9a8e0a4ed98d48a8fc6d21e9eb
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07622492B2

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