Реакция #1267678

Уравнение реакции

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

Выход 64.9%

Растворители

N,N-dimethylformamide

Условия реакции

Обработка

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
   Экстракцияextracted 2× with ethyl acetate
4. 4
   ПромывкаThe combined organic layers were washed with water
5. 5
   Сушкаdried over magnesium sulfate
6. 6
   Фильтрацияfiltered
7. 7
   Концентрированиеconcentrated in vacuo
8. 8
   workup.ADDITIONTo the residue was added aqueous 1N sodium hydroxide (10 mL) and ethyl alcohol (2 mL)
9. 9
   Температураthe mixture heated
10. 10
    Температураat reflux for 4.5 hours
11. 11
    ТемператураAfter cooling in an ice water bath
12. 12
    Другоеthe precipitate collected
13. 13
    Промывкаrinsed with water
14. 14
    Другоеdried
15. 15
    ДругоеRecrystallization from ethyl alcohol

Методика

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.

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