Sodium hydride → 5-{4-[5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-piperidin-1-yl}-biphenyl-2-carboxylic acid methyl ester

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Reaction Steps

A mixture of 5-(4-hydroxy-piperidin-1-yl)-biphenyl-2-carboxylic acid methyl ester (318 mg, 1.02 mmol), 4-bromomethyl-5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazole (375 mg, 1.08 mmol), and sodium hydride (52 mg, 1.30 mmol) in dimethylformamide (4 mL) is stirred at room temperature for 2.5 h. The mixture is partitioned between saturated aqueous ammonium chloride and ethyl acetate. The layers are separated and the aqueous layer is extracted with ethyl acetate (3×). The ethyl acetate layers are washed with brine (3×), dried (MgSO4), and concentrated under reduced pressure. The crude material is purified on silica (40 g) eluting with a gradient of ethyl acetate in heptane (0-60%) to provide the title compound (245 mg, 42%) as a glassy film. LC-ES/MS m/z 579.2 (M+1).

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