Ammonium Chloride → 6-{4-[5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid methyl ester

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Reaction Steps

Tetrahydrofuran (4 mL) is added at room temperature to a mixture of 18-crown-6 (306 mg, 1.14 mmole), tert-butyl alcohol, potassium derivative (134 mg, 1.14 mmole) and 6-(4-hydroxy-piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic acid methyl ester (300 mg, 1.040 mmole). The mixture is stirred for 15 minutes and then 4-bromomethyl-5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazole (361 mg, 1.04 mmole) is added. After 1.5 h, a saturated solution of NH4Cl is added and extracted with ethyl acetate. The organic layers are combined, dried over anhydrous sodium sulfate, filtered and the solvent is removed under reduced pressure. The residue is purified via flash chromatography (12 g silica) eluting with a gradient of hexane:ethyl acetate from 20% to 100% to provide the title compound (196 mg, 34%) as a white solid. ES/MS m/z 554.0 (M+1)

Provenance & Evidence