Acetic Acid → HCID 178500648, Verbindung

HRID 132463Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 132463
[Cl:1][C:2]1[C:10]2[C:5](=[C:6]([Cl:24])[CH:7]=[C:8]([CH2:13][C@@H:14]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[C:15]([O:17]C)=O)[C:9]=2[CH2:11]O)[NH:4][N:3]=1.S(Cl)(Cl)=O.[F:29][C:30]([F:34])([F:33])[CH2:31][NH2:32].C(=O)([O-])[O-].[K+].[K+].C(O)(=O)C>C(#N)C.C(OCC)(=O)C>[Cl:1][C:2]1[C:10]2[C:9]3[CH2:11][N:32]([CH2:31][C:30]([F:34])([F:33])[F:29])[C:15](=[O:17])[C@H:14]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[CH2:13][C:8]=3[CH:7]=[C:6]([Cl:24])[C:5]=2[NH:4][N:3]=1

Komponenten

8

Edukt 5

HCID 176Acetic AcidHCID 9773Ethanamine, 2,2,2-trifluoro-HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 178500726(S)-dimethyl 2-((3,7-dichloro-4-(hydroxymethyl)-1H-indazol-5-yl)methyl)succinate

Produkt 1

HCID 178500648HCID 178500648, VerbindungAusbeute 42 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

(S)-Dimethyl 2-((3,7-dichloro-4-(hydroxymethyl)-1H-indazol-5-yl)methyl)succinate (990 mg, 2.64 mmol) was dissolved in thionyl chloride (2.0 M in dichloromethane) (20 mL, 40.0 mmol). Mixture stirred at room temperature for 3 hours. Mixture was concentrated by roto-vap. Residue was dissolved in ethyl acetate. Mixture was washed twice with aqueous sodium bicarbonate. Organics were dried MgSO4, filtered and then concentrated to dryness. A portion of the residue (535 mg, 1.359 mmol) was dissolved in acetonitrile (15 mL). 2,2,2-Trifluoroethylamine (600 μl, 7.57 mmol) was added to the mixture followed by potassium carbonate (225 mg, 1.628 mmol). Mixture was warmed to reflux and held with stirring for 1 hour. Mixture was cooled to room temperature and then filtered over celite. Filtrate was concentrated by roto-vap. Residue was dissolved in toluene (15 mL). Acetic acid (500 μl, 8.73 mmol) was added to the mixture. Reaction was warmed to reflux and held with stirring for 14 hours. Mixture was cooled to room temperature and then diluted with ethyl acetate. Material was washed twice with aqueous sodium bicarbonate and the aqueous phase was discarded. Organics were dried MgSO4, filtered and then concentrated to dryness. Silica gel chromatography eluting ethyl acetate-hexanes afforded the title compound as off-white solid in 42% yield. MS (M+H)+=423.9, 425.9.

Aufarbeitung

  1. concentrationMixture was concentrated by roto-vap
  2. dissolutionResidue was dissolved in ethyl acetate
  3. washMixture was washed twice with aqueous sodium bicarbonate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. temperatureMixture was warmed
  7. temperatureto reflux
  8. stirringwith stirring for 1 hour
  9. temperatureMixture was cooled to room temperature
  10. filtrationfiltered over celite
  11. concentrationFiltrate was concentrated by roto-vap
  12. dissolutionResidue was dissolved in toluene (15 mL)
  13. customReaction
  14. temperaturewas warmed
  15. temperatureto reflux
  16. stirringwith stirring for 14 hours
  17. temperatureMixture was cooled to room temperature
  18. washMaterial was washed twice with aqueous sodium bicarbonate
  19. filtrationfiltered
  20. concentrationconcentrated to dryness
  21. washSilica gel chromatography eluting ethyl acetate-hexanes

Quellen und Nachweise

ORD-Eintrag
ord-ffb95f07bfde42c3892f858345957ccb
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07384931B2

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