Sodium hydride → Tert-butyl 4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperidine-1-carboxylate

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Reaction Conditions

Reaction Steps

Tert-butyl 4-(4-hydroxyphenyl)piperidine-1-carboxylate (364 mg, 1.31 mmol) was dissolved in DMF (10 ml). To the solution, sodium hydride (58 mg, 1.44 mmol) was added at room temperature, and the solution was stirred for 20 minutes at 80° C. To the solution, 2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazole prepared in Example 6 (300 mg, 1.38 mmol) was added with cooling on ice-bath followed by stirring for further 20 minutes at 80° C. To the reaction mixture, ice-water was added, and the solution was stirred vigorously. The precipitates were filtered off, washed with water and dissolved in methylene chloride. The organic phase was washed with a saturated saline solution, dried over magnesium sulfate and then filtered. The resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/methanol=200/1) and then crystallized from methylene chloride-diisopropyl ether to afford tert-butyl 4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperidine-1-carboxylate (248 mg, yield 41%) as a white powder.

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