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

HRID 1437867Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1437867
[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.[F:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[NH:23][N:24]=CC.N1C=CC=CC=1.Cl.O1CCOCC1>ClCCCl.C(O)(=O)C>[F:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[N:23]1[C:11](=[O:12])[C:4]2[C@@H:5]3[C:8]([CH3:10])([CH3:9])[C@@:2]([CH3:1])([CH2:7][CH2:6]3)[C:3]=2[NH:24]1

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 312751,4-DioxaneHCID 57941306(1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride2×HCID 69017434HCID 69017434, Verbindung2×

Produkt 1

HCID 57941339(4s,7r)-2-(2,4-Difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-oneAusbeute 45,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittel2×HCID 176Acetic AcidLösungsmittel

Versuchsvorschrift

A solution of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 5.4 g, 25.15 mmol) in 1,2-dichloroethane (60 mL) was added over a period of 1 min to a cooled (0° C.) solution of N-(2,4-difluoro-phenyl)-N′-ethylidene-hydrazine (Intermediate 26; 3.92 g, 23.04 mmol) and pyridine (2.9 mL, 35.9 mmol) in 1,2-dichloroethane (30 mL). The reaction mixture was stirred at room temperature for 15 min and then at 50° C. for 40 min. The reaction mixture was cooled, and a solution of HCl in dioxane (4 M, 18 mL, 72 mmol) was added. The solution was stirred for 5 min at room temperature and then glacial acetic acid (30 mL) was added. The reaction mixture was stirred at 100° C. for 45 min. The solvent was evaporated and 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 (2×50 mL). The combined organic layers were washed with brine (100 mL), dried (magnesium sulfate), filtered, evaporated and eluted through a plug of silica gel with 30% ethyl acetate/hexanes to give (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (3.2 g, 45%) as an orange gummy solid.

Aufarbeitung

  1. waitat 50° C. for 40 min
  2. temperatureThe reaction mixture was cooled
  3. stirringThe solution was stirred for 5 min at room temperature
  4. stirringThe reaction mixture was stirred at 100° C. for 45 min
  5. customThe solvent was evaporated
  6. additiondichloromethane (200 mL) was added
  7. washThe solution was washed with 50% saturated brine (2×50 mL)
  8. extractionthe combined aqueous layers were back-extracted with dichloromethane (2×50 mL)
  9. washThe combined organic layers were washed with brine (100 mL)
  10. dry with materialdried (magnesium sulfate)
  11. filtrationfiltered
  12. customevaporated
  13. washeluted through a plug of silica gel with 30% ethyl acetate/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-4afd2f1abd0b452c891b19c8516b5375
Quelldatensatz
uspto-grants-2009_11
Patentnummer
US07622492B2

Notizen zur Reaktion

Wird geladen…