Lithium Hydroxide → 3-{[4-(4,5-Difluorobenzofuran-7-yl)-2-fluoro-phenoxy]methyl}benzoic acid

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Reaction Conditions

Reaction Steps

1,4-Dioxane (12 mL) and water (4 mL) were added to 2-fluoro-4-hydroxyphenylboronic acid (475 mg, 3.0 mmol), 7-bromo-4,5-difluoro-1-benzofuran (590 mg, 2.53 mmol), sodium carbonate (540 mg, 5.1 mmol), and Pd(dppf)Cl2 (catalytic amount), and stirred at 100° C. for 2 hours. The reaction solution was concentrated under reduced pressure. To the residue, ethyl acetate and 1 N hydrochloric acid were added and stirred. After that, the insoluble material was filtered off, and extraction was performed with ethyl acetate. The organic phase was washed with saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. Then, to the resulting residue, methyl 3-(bromomethyl)benzoate (595 mg, 2.6 mmol), potassium carbonate (414 mg, 3.0 mmol), and DMF (4 mL) were added, and stirred overnight. After diluted with ethyl acetate, the resultant was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure. To the resulting residue, methanol (5 mL), water (2 mL), THF (5 mL), and lithium hydroxide (210 mg, 5.0 mmol) were added, and stirred at room temperature overnight. The reaction solution was concentrated under reduced pressure, and extraction was performed with ethyl acetate. The organic phase was washed with saturated brine, and then dried over anhydrous magnesium sulfate. After the solvent was distilled away under reduced pressure, the resulting solid was collected by filtration to thus obtain the title compound.

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