Water → 1-[4-(2-Aminopyridin-4-yloxy)-2-fluorophenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester

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Reaction Steps

1-[4-(2-Carbamoylpyridin-4-yloxy)-2-fluorophenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester (10 g) was dissolved in N,N-dimethylformamide (100 ml) at room temperature, and water (2.41 ml) was added. Iodobenzene diacetate (7.91 g) was added with stirring at room temperature, the reaction mixture was stirred for 3 hours, iodobenzene diacetate (360 mg) was further added, and the reaction mixture was stirred for 2 hours. Ethyl acetate (100 ml) and a 5% aqueous solution of sodium hydrogencarbonate (100 g) were added to the reaction mixture, and layers were separated. The organic layer was washed with water, dried over magnesium sulfate, filtered, and concentrated. Ethyl acetate (30 ml) was added to the resultant crude crystals, and the mixture was heated and stirred at 60° C. After confirming the crystals were dissolved, the mixture was allowed to cool down to room temperature. Seed crystals obtained in Method 1 (50 mg) were added, and the mixture was stirred for 30 minutes. After confirming the precipitation of the crystals, heptane (100 ml) was added, and the mixture was further stirred for 30 minutes. The crystals were collected by filtration and dried to give the title compound (6.84 g).

Provenance & Evidence