反应详情

To a suspension of (Z)-5-fluoro-4-[1-iodo-3-oxo-3-(1H-pyrrol-2-yl)-propenyl]-1,3-dihydro-indol-2-one (from Example 8 above) (198 mg, 0.5 mmol) in 1,3-propanediol (Fluka, 7.0 g, 92 mmol) was added NaH (Aldrich, 60%, 0.5 g, 12.5 mmol) in portions at room temperature. After stirring at room temperature for 30 minutes, the reaction mixture was heated to 110° C. for 2.5 hours. The reaction was quenched by pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (50 mL) and extracted with ethyl acetate (3×50 mL). The combined organic extracts were successively washed with water (20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography (silica gel, 50% ethyl acetate in hexanes) to afford 6-fluoro-5-(3-hydroxy-propoxy)-3-(1H-pyrrol-2-yl)-1H-benzo[cd]indol-2-one as a yellow solid. (Yield 51.5 mg, 31.6%).

1. temperaturethe reaction mixture was heated to 110° C. for 2.5 hours
2. customThe reaction was quenched
3. additionby pouring the reaction mixture into an ice-cold saturated aqueous ammonium chloride solution (50 mL)
4. extractionextracted with ethyl acetate (3×50 mL)
5. washThe combined organic extracts were successively washed with water (20 mL) and brine (20 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by flash chromatography (silica gel, 50% ethyl acetate in hexanes)