Reaktion #439089

Reaktionsgleichung

2-fluoroaniline

hydrochloric acid

4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid

triethylamine

ethyl chloroformate

→

N-(2-fluorophenyl)-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamide

Ausbeute 64.9%

Lösungsmittel

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe mixture was stirred for an additional 45 minutes
2. 2
   workup.STIRRINGto stir at ambient temperature for 14 hours
3. 3
   Extraktionextracted 2× with ethyl acetate
4. 4
   WaschenThe combined organic layers were washed with water
5. 5
   Trocknendried over magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated in vacuo
8. 8
   workup.ADDITIONTo the residue was added aqueous 1N sodium hydroxide (10 mL) and ethyl alcohol (2 mL)
9. 9
   Temperaturthe mixture heated
10. 10
    Temperaturat reflux for 4.5 hours
11. 11
    TemperaturAfter cooling in an ice water bath
12. 12
    Sonstigethe precipitate collected
13. 13
    Waschenrinsed with water
14. 14
    Sonstigedried
15. 15
    SonstigeRecrystallization from ethyl alcohol

Vorschrift

To a solution of 4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid (538 mg, 3 mmol) and triethylamine (0.88 mL, 6.3 mmol) in N,N-dimethylformamide (15 mL) at 0° C. was added ethyl chloroformate (0.57 mL, 6 mmol). After stirring at 0° C. for 45 minutes, 2-fluoroaniline (0.58 mL, 6 mmol) wad added. The mixture was stirred for an additional 45 minutes, then allowed to stir at ambient temperature for 14 hours. The mixture was poured into aqueous 1.2 N hydrochloric acid and extracted 2× with ethyl acetate. The combined organic layers were washed with water, dried over magnesium sulfate, filtered, and concentrated in vacuo. To the residue was added aqueous 1N sodium hydroxide (10 mL) and ethyl alcohol (2 mL) and the mixture heated at reflux for 4.5 hours. After cooling in an ice water bath, the mixture was acidified with aqueous hydrochloric acid, the precipitate collected, rinsed with water and dried. Recrystallization from ethyl alcohol afforded N-(2-fluorophenyl)-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamide (Compound 46)(530 mg). mp 238-240° C.

Quelle