tert-Butanol → 4-Benzyl-6-(4-[1,2,4]oxadiazol-5-yl-phenyl)-[1,4]oxazepane

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Reaction Steps

To a mixture of 4-(4-benzyl-[1,4]oxazepan-6-yl)-benzonitrile (1.0 g, 3.4 mmol) in tert-butyl alcohol (10 mL) at room temperature was added finely powdered potassium hydroxide (2.0 g, 30 mmol) and the resulting mixture was refluxed for 3 hours with vigorous stirring. After cooling to room temperature, the reaction mixture was diluted with water and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated. The resulting residue was dissolved in dimethylformamide dimethylacetal (3 mL) at room temperature. The solution was heated to 110° C. and stirred for one hour. After removal of excess dimethylformamide dimethylacetal under reduced pressure, the residual oil was dissolved in 1,4-dioxane (3 mL). To the resulting mixture at room temperature was added hydroxylamine hydrochloride (0.09 g, 1.3 mmol), acetic acid (3 mL) and 1M aqueous solution of sodium hydroxide (1.5 mL) and the mixture was refluxed for 2 hours. After cooling to room temperature, the reaction mixture was poured into water and extracted with ethyl acetate. The organic extracts were dried over anhydrous sodium sulfate and concentrated. Purification of the residue by flash column chromatography on silica gel (hexane/ethyl acetate=80/20 to 50/50 as an eluant) was performed to yield 4-benzyl-6-(4-[1,2,4]oxadiazol-5-yl-phenyl)-[1,4]oxazepane as colorless oil (0.03 g, 0.11 mmol, 8%).

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