反应详情

Sodium hydride (60%, 93 mg, 1.2 equiv, 2.3 mmole) is added at room temperature under nitrogen atmosphere to a solution of 6-(4-hydroxy-piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic acid methyl ester (557 mg, 1.00 equiv, 1.93 mmole), tetra-n-butylammonium iodide (73 mg, 0.1 equiv, 193 μmoles) and 4-bromomethyl-3-(2,6-dichloro-phenyl)-5-isopropyl-isoxazole (674 mg, 1 equiv, 1.93 mmole) in anhydrous tetrahydrofuran (6 mL). The reaction mixture is stirred for 6 h. Aqueous saturated NH4Cl is added and the resulting aqueous solution is extracted with ethyl acetate. The organic layers are combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified via flash chromatography (40 g silica) eluting with a gradient of ethyl acetate:hexane (10% to 100%) to provide the title compound as a white solid (205 mg, 19%). ES/MS m/z 556.0 (M+1)

1. extractionthe resulting aqueous solution is extracted with ethyl acetate
2. dry with materialdried over anhydrous sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. customThe residue is purified via flash chromatography (40 g silica)
6. washeluting with a gradient of ethyl acetate