反应详情

To a stirred suspension of NaH (260 mg of 60 wt % in mineral oil, 6.50 mmol) in DMF (5 mL) under an atmosphere of dry nitrogen was added 1H-indole-2,6-dicarboxylic acid diethyl ester (see Example 1) (1.50 g, 5.74 mmol) in DMF (40 mL) over 5 min. Ethyl 4-bromobutyrate (1.40 g, 7.2 mmol) was added dropwise, and the reaction was stirred at room temperature for 20 h. The reaction was quenched with water and extracted into methylene chloride (3×50 mL). The combined organic extracts were washed with brine, dried over MgSO4, and concentrated. The crude tri-ester intermediate was taken up in dry THF (30 mL) and to this solution was added potassium tert-butoxide (20 mL of a 1.0 M solution in THF, 20 mmol). After stirring at room temperature for 16 h, the reaction was quenched with water (60 mL) and concentrated HCl (75 mL) and refluxed for 5 h. The resulting suspension was cooled, filtered, then washed with water followed by hexanes. The resulting solid was dried in a vacuum oven to give 9-oxo-6,7,8,9-tetrahydro-pyrido[1,2-a]indole-3-carboxylic acid (1.25 g, 95%) as an analytically pure purple powder.

1. customThe reaction was quenched with water
2. extractionextracted into methylene chloride (3×50 mL)
3. washThe combined organic extracts were washed with brine
4. dry with materialdried over MgSO4
5. concentrationconcentrated
6. additionwas added potassium tert-butoxide (20 mL of a 1.0 M solution in THF, 20 mmol)
7. stirringAfter stirring at room temperature for 16 h
8. customthe reaction was quenched with water (60 mL) and concentrated HCl (75 mL)
9. temperaturerefluxed for 5 h
10. temperatureThe resulting suspension was cooled
11. filtrationfiltered
12. washwashed with water
13. customThe resulting solid was dried in a vacuum oven