Hydrochloric Acid → 1-{3-Fluoro-4-[(phenylmethyl)oxy]phenyl}-4-hydroxy-1H-indole-6-carbonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-bromo-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indole-6-carbonitrile (D13) (400 mg, 0.95 mmol) in dioxane (6 mL) and water (6 mL) was added potassium hydroxide (216 mg, 3.9 mmol). The reaction mixture was degassed with argon and then treated with 2-di-tert-butylphosphino-2′,4′,6′-trisisopropylbiphenyl (22 mg, 0.05 mmol) and tris(dibenzylideneacetone)dipalladium (0) (19 mg, 0.02 mmol). After heating at 85° C. for 1 hour, the mixture was allowed to cool to room temperature and then diluted with ethyl acetate and water. The pH was adjusted to 7 by the addition of 1M hydrochloric acid. The organic phase was dried over magnesium sulphate, filtered and concentrated in vacuo. The product was purified by silica gel chromatography eluting with 2-60% ethyl acetate in hexane to yield the title compound (D14), (323 mg).

Provenance & Evidence