反应详情

To a stirred solution of 4-oxo-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid (155 mg, 0.75 mmol) and triethylamine (209 μL, 1.5 mmol) in dimethylformamide (4 mL) at 0° C. was added ethyl chloroformate (143 μL, 1.5 mmol). After stirring an additional 45 minutes, 2-fluoroaniline (145 μL, 1.5 mmol) was added. The reaction mixture was stirred for 30 minutes, then poured into aqueous 3.6N 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 5N sodium hydroxide (5 mL) and ethyl alcohol (1 mL), and the mixture was heated at reflux for 30 minutes. After cooling in an ice water bath, the reaction mixture was acidified with hydrochloric acid, the precipitate was collected, rinsed with water, and dried to give 55 mg of N-(2-fluorophenyl)-4-oxo-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indole-3 oxamide (Compound 2).

1. stirringThe reaction mixture was stirred for 30 minutes
2. extractionextracted 2× with ethyl acetate
3. washThe combined organic layers were washed with water
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. additionTo the residue was added aqueous 5N sodium hydroxide (5 mL) and ethyl alcohol (1 mL)
8. temperaturethe mixture was heated
9. temperatureat reflux for 30 minutes
10. temperatureAfter cooling in an ice water bath
11. customthe precipitate was collected
12. washrinsed with water
13. customdried