Sodium Bicarbonate → 5-Benzyloxy-2-methylpyridine 1-oxide

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Reaction Steps

To a solution of 5-benzyloxy-2-methyl pyridine described in Preparation Example 182 (5.99 g, 30.1 mmol) in methylene chloride (100 mL) was added 3-chloroperoxylbenzoic acid (8.79 g, 33.1 mmol, 65%) at 0° C., and the solution was stirred at room temperature for 2 hours. An aqueous solution of saturated sodium bicarbonate was added to the reaction solution at 0° C., which was partitioned with methylene chloride. This organic layer was separated, washed with an aqueous solution of saturated sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. The organic layer was filtered, then, the solvent was evaporated in vacuo, and 5-benzyloxy-2-methyl-pyridine-1-oxide (7.71 g) was obtained as a crude product of a white solid. Next, acetic anhydride (77 mL) was added to 5-benzyloxy-2-methyl-pyridin-1-oxide (7.71 g), and the solution was stirred for 80 minutes at 120° C. This reaction mixture was cooled to room temperature, then, the solvent was evaporated in vacuo. Ethanol (50 mL) and an aqueous solution of 5N sodium hydroxide (7 mL) were added to the resulting residue, and the solution was stirred at room temperature for 50 minutes. The solvent was evaporated in vacuo, this residue was partitioned in brine and ethyl acetate. The organic layer was separated, washed with brine and dried over anhydrous magnesium sulfate. The organic layer was filtered, then, the solvent was evaporated in vacuo, the residue was purified by NH silica gel column chromatography (heptane/ethyl acetate=1/1), and the title compound (4.17 g, 54%) was obtained as a white solid.

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