18-Crown-6 → Tert-butyl 4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)piperidine-1-carboxylate

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Reaction Steps

To a solution of 13.05 g (64.83 mmol) of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester in THF (120 mL) is added at 0° C. (ice bath) 18-crown-6 (19.6 g, 73.48 mmol) and potassium tertiary butoxide (8.68 g, 73.48 mmol). The resulting mixture is stirred for 20 min at room temperature, and added dropwise to a solution of 4-bromomethyl-5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazole (15 g, 43.22 mmol) in 75 mL of THF. The resulting mixture was stirred at room temperature for 14 h. To the reaction mixture is added water (500 mL), and it is extracted with EtOAc (3×200 mL). The organics are washed with brine (2×250 mL), dried (Na2SO4), filtered and concentrated to afford a crude which is purified by flash chromatography eluting with Hexanes/EtOAc 8:2, to obtain the title compound as a pale yellow oil (16 g (79%)). MS (m/e): 467 (M+1)

Provenance & Evidence