Boric Acid → Methyl 2-(2,3'-dicyano-4'-hydroxybiphenyl-4-yl)isonicotinate

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Reaction Steps

1.32 g of methyl 2-[4′-(benzyloxy)-2,3′-dicyanobiphenyl-4-yl]isonicotinate, which had been obtained in the same manner as in Preparation Example 8(1) using 4-(benzyloxy)-3-cyanophenyl]boric acid and methyl 2-(3-cyano-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)isonicotinate, was dissolved in a mixture of 50 ml of THF and 50 ml of methanol, and 0.5 g of palladium-carbon was added, followed by stirring in a hydrogen atmosphere at room temperature for 12 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to obtain 0.5 g of methyl 2-(2,3′-dicyano-4′-hydroxybiphenyl-4-yl)isonicotinate. (2) 230 mg of this compound was dissolved in DMF, and 50 μL of iodomethane and 108 mg of potassium carbonate were added, followed by stirring at room temperature for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried and concentrated under reduced pressure. Chloroform was added to the residue, and the precipitated crystal was collected by filtration, followed by washing with chloroform to obtain 73 mg of methyl 2-(2,3′-dicyano-4′-methoxybiphenyl-4-yl)isonicotinate. (3) 73 mg of this compound was dissolved in 2 ml of methanol and 2 ml of THF, and 220 μL of an aqueous 1 M sodium hydroxide solution was added, followed by heating at 60° C. for 2 hours. After cooling, the solvent was removed under reduced pressure, and then water was added to the residue, followed by neutralization with 1 M hydrochloric acid. The precipitated crystal was collected by filtration and washed with a mixture of ethanol and water to obtain 64 mg of 2-(2,3′-dicyano-4′-methoxybiphenyl-4-yl)isonicotinic acid.

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