m-Chloroperbenzoic acid → 3-Ethoxy-4-(2-ethoxyethoxy)pyridine-2-carbaldehyde

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Reaction Steps

3-Ethoxy-4-(2-ethoxyethoxy)-2-methylpyridine (0.92 g, 4.09 mmol, obtained from Example 4(c)) dissolved in CH2Cl2 (5 mL) was added dropwise to m-CPBA (1.33 g, 4.50 mmol) in CH2Cl2 (5 mL) at 0° C. The reaction mixture was stirred at r.t. for 16 h. CH2Cl2 (10 mL) was then added and the organic phase was washed with sodium carbonate (5% aq., 2×20 mL), dried (MgSO4) and evaporated in vacuo. The residue was dissolved in acetic anhydride (20 mL) and stirred at 130° C. for 1 h. The solvent was evaporated in vacuo and water (40 mL) was added to the residue. The pH was adjusted to pH 8 with 2M sodium hydroxide. The aqueous phase was extracted with CH2Cl2, dried (MgSO4) and evaporated. The residue was dissolved in ethanol (5 mL) and 2M sodium hydroxide (8 mL) was added. The mixture was stirred under reflux for 2 h. The solvent was evaporated and the residue partitioned between water and CH2Cl2. The organic phase was dried (MgSO4) and concentrated and the residue was dissolved in CH2Cl2 (10 mL) and manganese oxide (1.57 g, 18.06 mmol) was added. The mixture was then stirred under reflux under a nitrogen atmosphere overnight. The reaction mixture was filtrated through celite and concentrated, and the crude product was purified by flash chromatography (heptane/ethyl acetate; 1:1), giving the title compound (0.22 g, 22%).

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