1,4-Dioxane → Methyl 3-fluoro-11-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[b]quinoline-1-carboxylate

HRID 521413Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 521413
O=[C:2]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[C:9]([O:11]C)=O.[NH2:13][C:14]1[CH:15]=[C:16]([CH:21]=[C:22]([F:24])[CH:23]=1)[C:17]([O:19][CH3:20])=[O:18].O1CCOCC1>O>[F:24][C:22]1[CH:21]=[C:16]([C:17]([O:19][CH3:20])=[O:18])[C:15]2[C:9](=[O:11])[C:3]3[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:2]=3[NH:13][C:14]=2[CH:23]=1

Komponenten

5

Edukt 3

HCID 312751,4-DioxaneHCID 288225Methyl 2-oxocycloheptane-1-carboxylateHCID 3807862Methyl 3-amino-5-fluorobenzoate

Produkt 1

HCID 89669535Methyl 3-fluoro-11-oxo-6,7,8,9,10,11-hexahydro-5H-cyclohepta[b]quinoline-1-carboxylateAusbeute 107,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A mixture of methyl 2-oxocycloheptanecarboxylate (0.34 g, 2 mmol), methyl 3-amino-5-fluorobenzoate (0.33 g, 2 mmol), polyphosphoric acid (4.0 g) and dioxane (5 mL) was heated at 130° C. for 5 hours. After cooling to room temperature, the solution was diluted with water (100 mL), and NaOAc.3H2O (7.3 g) was added. Then the resulting precipitate was collected by filtration and dried. The solid was suspended in methanol (20 mL) and SOCl2 (10 mL) was added, the mixture was stirred at reflux for 5 hours, concentrated and treated with water (50 mL), extracted with ethyl acetate (3×50 mL). The organic layer was separated, concentrated and the residue was chromatographed to give the crude product (0.62 g). MS (ESI) m/e [M+1]+290.0.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. additionwas added
  3. filtrationThen the resulting precipitate was collected by filtration
  4. customdried
  5. additionSOCl2 (10 mL) was added
  6. temperatureat reflux for 5 hours
  7. concentrationconcentrated
  8. additiontreated with water (50 mL)
  9. extractionextracted with ethyl acetate (3×50 mL)
  10. customThe organic layer was separated
  11. concentrationconcentrated
  12. customthe residue was chromatographed

Quellen und Nachweise

ORD-Eintrag
ord-a937d8b4fc3f45eb803ae03ae362bce1
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09328111B2

Notizen zur Reaktion

Wird geladen…