反应详情

温度

90 °C

To a solution of 4-bromo-6-fluoro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indole (D17) (980 mg, 2.366 mmol) in 1,4-dioxane (20 mL) and water (20 mL) was added potassium hydroxide (531 mg, 9.46 mmol). The reaction mixture was purged with argon and then treated with 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (60.3 mg, 0.142 mmol) and tris(dibenzylideneacetone)dipalladium(0) (43.3 mg, 0.047 mmol). The reaction mixture was heated at 90° C. for 1 hour. After cooling to room temperature, the mixture was diluted with ethyl acetate and water. The pH was adjusted to ˜7 by the addition of 1M hydrochloric acid. After separation of the layers, the aqueous phase was re-extracted with ethyl acetate. The combined organic layers were dried over magnesium sulphate, filtered and concentrated. The product was purified by silica gel chromatography eluting with 5-40% ethyl acetate in hexane to yield the title compound (D18), (382 mg).

1. customThe reaction mixture was purged with argon
2. temperatureAfter cooling to room temperature
3. customAfter separation of the layers
4. extractionthe aqueous phase was re-extracted with ethyl acetate
5. dry with materialThe combined organic layers were dried over magnesium sulphate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe product was purified by silica gel chromatography
9. washeluting with 5-40% ethyl acetate in hexane