Hydrochloric Acid → 5-Fluoro-3-hydroxy-6-methoxy-quinoline-4-carbaldehyde

Participants

Reaction Steps

Tris(dibenzylideneacetone)dipalladium(0) (40 mg, 0.04 mmol, 0.02 eq) is added at room temperature to a stirred solution of 3-chloro-5-fluoro-6-methoxy-quinoline-4-carbaldehyde (500 mg, 2.10 mmol, 1.0 eq) in dioxane (6 mL), followed by 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (100 mg, 0.21 mmol, 0.1 eq) and a 1.6 M potassium hydroxide aqueous solution (2 mL). The reaction mixture is irradiated by microwaves at 125° C. for 15 minutes, then water (10 mL) is added, the resulting mixture is neutralized with 2.0 N hydrochloric acid aqueous solution and extracted with ethyl acetate (3×10 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a crude product that is purified by column chromatography (silica gel, eluent: petroleum ether:ethyl acetate, 5:1, v/v) to afford 5-fluoro-3-hydroxy-6-methoxy-quinoline-4-carbaldehyde as a light yellow solid (168 mg, 36% yield).

Provenance & Evidence