18-Crown-6 → 4-[5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-azepane-1-carboxylic acid tert-butyl ester

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Reaction Steps

To a solution of 4-hydroxy-azepane-1-carboxylic acid tert-butyl ester (1.88 g, 8.73 mmol) in anhydrous THF (15 mL) at 0° C. is added 18-crown-6 (2.3 g, 8.70 mmol) and tert-butyl alcohol, potassium derivative (8.8 mL, 1.0 M, 8.80 mmol). The mixture is stirred at room temperature for 20 minutes following which 4-bromomethyl-5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazole (1.8 g, 5.19 mmol) in THF is added over 2 minutes. The mixture is stirred for 2 h and water (10 mL) is added. The mixture is concentrated under reduced pressure and extracted with ethyl acetate (3×). The combined ethyl acetate layers are dried (MgSO4), concentrated, and purified via flash chromatography (120 g silica) eluting with a gradient of ethyl acetate in heptane (0 to 60%) to provide the title compound (420 mg, 17%).

Provenance & Evidence