Acetic Acid → HCID 23153143, compound

Participants

Reaction Steps

To a solution of 1-benzylpiperazine (0.500 ml) in methanol (25 ml) were added 1-Boc-azetidin-3-one (495 mg), acetic acid (0.182 ml), followed by stirring at room temperature for 5 min. 10% palladium on carbon (308 mg) was added thereto, followed by stirring at room temperature under a hydrogen atmosphere for 15 hr. The catalyst was removed by filtration. The residue was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. This was concentrated to provide a crude product of 4-benzyl-1-(1-Boc-azetidin-3-yl)piperazine (ESI-MS (m/z): 332 [M+H]+). This was dissolved in tetrahydrofuran (10 ml). Lithium aluminum hydride (219 mg) was added thereto while stirring in an ice bath. The mixture was stirred under a nitrogen atmosphere in an ice bath for 15 min, at room temperature for 15 min, and was heated to reflux at 100° C. for 3.5 hr. The reaction mixture was cooled in an ice bath. Water (0.22 ml), a 5N aqueous solution of sodium hydroxide (0.22 ml) and water (1.1 ml) were added thereto, followed by stirring in an ice bath for 1 hr. Insoluble matter was removed by filtration. To the filtrate was added a 4N solution of hydrochloric acid in ethyl acetate (2.17 ml), which was concentrated to provide a crude product of 4-benzyl-1-(1-methylazetidin-3-yl)piperazine trihydrochloride (ESI-MS (m/z): 246[M+H]+). This was dissolved in water (25 ml) and 2-propanol (25 ml). 10% palladium on carbon (615 mg) was added thereto, followed by stirring under a hydrogen atmosphere at room temperature for 12 hr. The catalyst was removed by filtration. Concentration of the filtrate provided a crude product of the titled compound as a white solid (382 mg).

Provenance & Evidence