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温度

0 °C

In methylene chloride (30 ml) was dissolved 5-fluoro-1-methylindole-3-carboxylic acid (885 mg, 4.58 mmol). To the resulting solution was added oxalyl chloride (600 μl, 6.87 mmol) under stirring at 0° C., and the resulting mixture was stirred at room temperature for 1 hour. From the reaction mixture, the solvent was distilled off under reduced pressure. The residue was dissolved in methylene chloride (50 ml). The resulting solution was added dropwise to a solution of ethyl (4-amino-5-chloro-2-fluorophenyl)acetate (1.06 g, 4.58 mmol) in methylene chloride (20 ml), followed by heating under reflux for 15 minutes. The reaction mixture was cooled and triethylamine (3.19 ml, 22.9 mmol) was added thereto. The resulting mixture was heated under reflux for 18 hours. The reaction mixture was cooled and poured in 1N HCl, followed by extraction with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from hexane/ethyl acetate (2/1) eluate fractions, ethyl (5-chloro-2-fluoro-4-(((5-fluoro-1-methyl-3-indolyl)carbonyl)amino)phenyl)acetate (868 mg, 47%) was obtained as a white solid.

1. stirringthe resulting mixture was stirred at room temperature for 1 hour
2. distillationFrom the reaction mixture, the solvent was distilled off under reduced pressure
3. dissolutionThe residue was dissolved in methylene chloride (50 ml)
4. temperatureby heating
5. temperatureunder reflux for 15 minutes
6. temperatureThe reaction mixture was cooled
7. temperatureThe resulting mixture was heated
8. temperatureunder reflux for 18 hours
9. temperatureThe reaction mixture was cooled
10. extractionfollowed by extraction with ethyl acetate
11. dry with materialThe extract was dried over anhydrous sodium sulfate
12. distillationdistilled under reduced pressure
13. customto remove the solvent
14. customThe residue was purified by chromatography on a silica gel column, whereby from hexane/ethyl acetate (2/1) eluate fractions