Hydrochloric Acid → 6-Fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

HRID 245220

Reaktionsgleichung

Reaktionsgleichung von HRID 245220
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=O.[OH-].[K+].N1C2C(=CC=CC=2)C(=O)C1=[O:17].[F:26][C:27]([F:39])([F:38])[C:28]1[CH:29]=[C:30]([C:34](=O)[CH2:35][CH3:36])[CH:31]=[CH:32][CH:33]=1.Cl>C(O)C.O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]=[C:34]([C:30]1[CH:31]=[CH:32][CH:33]=[C:28]([C:27]([F:26])([F:38])[F:39])[CH:29]=1)[C:35]([CH3:36])=[C:5]2[C:6]([OH:11])=[O:17]

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 7054IsatinHCID 14797Potassium HydroxideHCID 137064Propiophenone, 3'-(trifluoromethyl)HCID 2365665-Fluoroisatin

Produkt 1

HCID 673838086-Fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acidAusbeute 91 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

5-Fluoroisatin (61.3 g, 371 mmol) was dissolved in ethanol (564 mL) to provide a dark red solution. KOH (125 g, 2226 mmol) was dissolved in water (226 mL) and the solution was added slowly to the isatin solution. 1-[3-(Trifluoromethyl)phenyl]-1-propanone (75 g, 371 mmol) was added, and the solution was heated to reflux for 1 h. The reaction mixture was cooled in an ice bath and neutralized with concentrated HCl (208 mL, 2597 mmol). The precipitate was collected by filtration, washed with water (100 mL), and air dried. The solid material was crushed and resuspended in 1:1 ethanol/water (800 mL). The slurry was refluxed for 30 min. The solid was collected by filtration, washed with 1:1 ethanol/water (100 mL), and dried. The solid material was crushed and resuspended in 1:1 ethanol/water (800 mL). The slurry was refluxed for 30 min. The solid was collected by filtration, washed with 1:1 ethanol/water (100 mL), and dried in a vacuum oven at 50° C. for 6 h to afford 6-fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (118.3 g, 91% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 14.41 (br. s., 1H), 8.19 (dd, J=5.65, 9.16 Hz, 1H), 7.94-8.00 (m, 2H), 7.89 (d, J=8.03 Hz, 1H), 7.72-7.81 (m, 2H), 7.53 (dd, J=2.76, 9.79 Hz, 1H), 2.41 (s, 3H); MS (m/z) 350.1 (M+H+).

Aufarbeitung

  1. customto provide a dark red solution
  2. temperaturethe solution was heated
  3. temperatureto reflux for 1 h
  4. filtrationThe precipitate was collected by filtration
  5. washwashed with water (100 mL), and air
  6. customdried
  7. customThe solid material was crushed
  8. temperatureThe slurry was refluxed for 30 min
  9. filtrationThe solid was collected by filtration
  10. washwashed with 1:1 ethanol/water (100 mL)
  11. customdried
  12. customThe solid material was crushed
  13. temperatureThe slurry was refluxed for 30 min
  14. filtrationThe solid was collected by filtration
  15. washwashed with 1:1 ethanol/water (100 mL)
  16. customdried in a vacuum oven at 50° C. for 6 h

Quellen und Nachweise

ORD-Eintrag
ord-1018117bbd8844c1b018be4dddd65b39
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658636B2

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