Реакция #332402

Уравнение реакции

1-[3-(Trifluoromethyl)phenyl]-1-propanone

KOH

5-Fluoroisatin

HCl

isatin

→

6-fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

Выход 91.0%

Растворители

water

ethanol

Условия реакции

Обработка

1. 1
   Другоеto provide a dark red solution
2. 2
   Температураthe solution was heated
3. 3
   Температураto reflux for 1 h
4. 4
   ФильтрацияThe precipitate was collected by filtration
5. 5
   Промывкаwashed with water (100 mL), and air
6. 6
   Другоеdried
7. 7
   ДругоеThe solid material was crushed
8. 8
   ТемператураThe slurry was refluxed for 30 min
9. 9
   ФильтрацияThe solid was collected by filtration
10. 10
    Промывкаwashed with 1:1 ethanol/water (100 mL)
11. 11
    Другоеdried
12. 12
    ДругоеThe solid material was crushed
13. 13
    ТемператураThe slurry was refluxed for 30 min
14. 14
    ФильтрацияThe solid was collected by filtration
15. 15
    Промывкаwashed with 1:1 ethanol/water (100 mL)
16. 16
    Другоеdried in a vacuum oven at 50° C. for 6 h

Методика

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+).

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