Benzyl 4-[(aminocarbonyl)(3,3-diethoxypropyl)amino]piperidin-1-carboxylate → HCID 68419696, compound

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Reaction Steps

A solution of benzyl 4-oxopiperidin-1-carboxylate (11.2 g), 3,3-diethoxypropane-1-amine (7.0 g), acetic acid (3 mL) and sodium triacetoxyborohydride (12.7 g) in dichloroethane (300 mL) was stirred at room temperature overnight. The reaction mixture was washed with an aqueous saturated sodium bicarbonate solution and saturated saline solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. A solution of the resulting residue and potassium isocyanate (3.4 g) in a mixture of methanol/acetic acid (190 mL/10 mL) was refluxed for 3 hours. Potassium isocyanate (3.4 g) was further added thereto and the mixture was refluxed for additional 1 hour. The solvent was distilled off under reduced pressure, and the residue was diluted with ethyl acetate and an aqueous saturated sodium bicarbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated saline solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (from ethyl acetate/hexane=4/1 to ethyl acetate) to obtain benzyl 4-[(aminocarbonyl)(3,3-diethoxypropyl)amino]piperidin-1-carboxylate (12.1 g, 62%) as a white powder. A solution of the resulting benzyl 4-[(aminocarbonyl)(3,3-diethoxypropyl)amino]piperidin-1-carboxylate (12.1 g) and 20% palladium on carbon (containing 50% water, 0.24 g) in methanol (300 mL) was stirred at room temperature overnight under a hydrogen atmosphere, and the catalyst was removed by filtration. The filtrate was concentrated under reduced pressure to obtain the title compound as a white powder.

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