Sodium hydride → 9-Oxo-6,7,8,9-tetrahydro-pyrido[1,2-a]indole-3-carboxylic acid

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Reaction Steps

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.

Provenance & Evidence