Acetic Acid → Benzyl 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)piperazine-1-carboxylate

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Reaction Steps

Benzyl 1-piperazinecarboxylate (5.00 g) and tert-butyl 4-oxopiperidine-1-carboxylate (4.52 g) were dissolved in methanol (100 ml), and acetic acid (2.34 ml) and 10% palladium on carbon (1.55 g) were added thereto, followed by stirring under a hydrogen atmosphere for 4 days. The catalyst was removed by filtration, and the filtrate was concentrated. To the residue were added acetone (50 ml) and water (50 ml) to dissolve, and sodium hydrogencarbonate (6.67 g) was added and stirred while cooling in an ice bath. Benzyl chloroformate (3.89 ml) was added thereto, followed by stirring in an ice bath for 3.5 hr. Part of the reaction mixture was concentrated, and ethyl acetate:tetrahydrofuran=1:1 (200 ml) and water (100 ml) were added thereto, followed by stirring at room temperature for 10 min. The organic layer was separated. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. This was concentrated, and the residue was purified by silica gel column chromatography (eluent; ethyl acetate, then ethyl acetate:methanol=50:1). Fractions containing the target compound were concentrated to provide the titled compound as a pale yellow oil (2.71 g, 29.6%).

Provenance & Evidence