Sodium Hydroxide → 4-(4-Amino-2,3-difluorophenoxy)pyridine-2-carboxamide

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Reaction Steps

The mixture of 4-amino-2,3-difluorophenol and 6-amino-2,3-difluorophenol (3.52 g) was dissolved in dimethyl sulfoxide (30 ml) under a nitrogen flow, and potassium tert-butoxide (1.49 g) was added at room temperature, followed by stirring for 30 min. 4-Chloropyridine-2-carboxamide (947 mg) was added thereto, followed by stirring at 80° C. for 6 hr. Then the reaction mixture was stirred at 100° C. for 14 hr. The reaction mixture was allowed to cool down to room temperature, and a 1N aqueous solution of sodium hydroxide (52.8 ml) was added, followed by stirring for 9 hr and 15 min. The reaction mixture was partitioned between ethyl acetate (300 ml) and water (300 ml). The aqueous layer was extracted with ethyl acetate (200 ml, twice), then the combined organic layer was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:3) and fractions containing the target compound were concentrated under reduced pressure. The residue was dried under reduced pressure to provide the titled compound as a pale brown solid (532 mg) which was a mixture of 4-(6-amino-2,3-difluorophenoxy)pyridine-2-carboxamide.

Provenance & Evidence