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 (17.9 g) was dissolved in N-methyl-2-pyrrolidone (125 ml) at room temperature, and water (7.2 ml) was added. Iodobenzene diacetate (14.1 g) was added with stirring at room temperature, followed by stirring for 4 hours and 7 minutes. Ethyl acetate (268 ml) and a 1N aqueous solution of sodium hydroxide (179 ml) were added to the reaction mixture, and the layers were separated. The organic layer was washed with a 5% aqueous solution of sodium chloride (179 ml) three times and water (179 ml) once, dried over magnesium sulfate, filtered, and concentrated. Toluene (72 ml) was added to the resultant crystals, and the mixture was heated and stirred at 90° C. After confirming the crystals were dissolved, the mixture was allowed to cool down to room temperature. The precipitated crystals were collected by filtration, washed with toluene (18 ml), and dried under reduced pressure at 50° C. for 4 hours to give the title compound (11.9 g) as pale orange crystals.

Provenance & Evidence