Phosphorus oxychloride → 4-Chloro-6,7-dimethoxyquinoline

HRID 331208

Reaktionsgleichung

Reaktionsgleichung von HRID 331208
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2O.P(Cl)(Cl)([Cl:18])=O>C(#N)C>[Cl:18][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:8][CH:7]=1

Komponenten

4

Edukt 2

HCID 24813Phosphorus oxychloride2×HCID 178486804HCID 178486804, Verbindung

Produkt 1

HCID 4596104-Chloro-6,7-dimethoxyquinolineAusbeute 73,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

A reactor was charged sequentially with 6,7-dimethoxy-quinoline-4-ol (1 L, 10.0 kg) and acetonitrile (64.0 L). The resulting mixture was heated to approximately 65° C. and phosphorus oxychloride (POCl3, 50.0 kg) was added. After the addition of POCl3, the temperature of the reaction mixture was raised to approximately 80° C. The reaction was deemed complete (approximately 9.0 hours) when <2% of the starting material remained (in process high-performance liquid chromatography [HPLC] analysis). The reaction mixture was cooled to approximately 10° C. and then quenched into a chilled solution of dichloromethane (DCM, 238.0 kg), 30% NH4OH (135.0 kg), and ice (440.0 kg). The resulting mixture was warmed to approximately 14° C., and phases were separated. The organic phase was washed with water (40.0 kg) and concentrated by vacuum distillation with the removal of solvent (approximately 190.0 kg). Methyl-t-butyl ether (MTBE, 50.0 kg) was added to the batch, and the mixture was cooled to approximately 10° C., during which time the product crystallized out. The solids were recovered by centrifugation, washed with n-heptane (20.0 kg), and dried at approximately 40° C. to afford the title compound (8.0 kg).

Aufarbeitung

  1. temperaturethe temperature of the reaction mixture was raised to approximately 80° C
  2. temperatureThe reaction mixture was cooled to approximately 10° C.
  3. customquenched into a chilled solution of dichloromethane (DCM, 238.0 kg), 30% NH4OH (135.0 kg), and ice (440.0 kg)
  4. temperatureThe resulting mixture was warmed to approximately 14° C.
  5. customphases were separated
  6. washThe organic phase was washed with water (40.0 kg)
  7. concentrationconcentrated by vacuum distillation with the removal of solvent (approximately 190.0 kg)
  8. additionMethyl-t-butyl ether (MTBE, 50.0 kg) was added to the batch
  9. temperaturethe mixture was cooled to approximately 10° C., during which time the product
  10. customcrystallized out
  11. customThe solids were recovered by centrifugation
  12. washwashed with n-heptane (20.0 kg)
  13. customdried at approximately 40° C.

Quellen und Nachweise

ORD-Eintrag
ord-d83b21da9c4c424f8a970bcfe82e8c35
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08877776B2

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