Hydrochloric Acid → 3-(6-Chloro-2-methoxypyridin-3-yl)-3-methylpiperidin-2-one

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To a stirred solution of methyl 2-(6-chloro-2-methoxypyridin-3-yl)-4-cyano-2-methylbutanoate (110 g, 390 mmol) and conc. HCl (60 mL) in MeOH (1 L) was added PtO2 (11 g) under N2. The suspension was degassed and refilled with H2 several times. Then the resulting mixture was stirred under 50 Psi of H2 at r.t for 16 hours. The reaction mixture was filtered and the combined filtrates were evaporated to dryness. To the above residue in MeOH (12 L) was added solid K2CO3 (2158 g, 15.6 mol) at r.t. The reaction mixture was heated at reflux for 16 hours. The reaction mixture was filtered, and the filter cake was washed with MeOH (5 L). The combined filtrates were evaporated to dryness, and the crude residue was partitioned between CH2Cl2 (10 L) and water (5 L). The aqueous layer was extracted with CH2Cl2 (5 L). The combined organic layers were washed with brine (5 L), dried over Na2SO4 and concentrated to dryness. The crude residue was triturated with MTBE to give 3-(6-chloro-2-methoxypyridin-3-yl)-3-methylpiperidin-2-one (770 g, 64%) as a white solid. 1H NMR was consistent with data described in the other synthetic route.

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