Piperazine → HCID 131724190, compound

Participants

Reaction Steps

To a mixture of 1-benzyl-3-(4-chloro-phenyl)-piperidin-4-one (15.2 g, 38.5 mmol) and piperazine (6.78 g, 77.1 mmol) in ethanol (6 mL) was added tetraisopropyl-orthotitanate (22.8 mL, 77.1 mmol) at room temperature. After stirring at room temperature for 3 days the reaction mixture was diluted with ethanol (250 mL) and sodium cyanoborohydride (5.10 g, 77.1 mmol) was added. The reaction mixture was stirred at room temperature for 24 h and was diluted with water (30 mL). The inorganic precipitate was filtered off and washed with ethanol and dichloromethane. The solvent was evaporated and the residue was taken up in ethylenglycol (100 mL) and sodium hydroxide (3.08 g, 77.1 mmol) was added. The reaction mixture was stirred at 130° C. for 15 min. After cooling water (200 mL) was added and the mixture was extracted four times with 200 mL tert.-butyl methyl ether. Organic phases were pooled, dried with magnesium sulfate and evaporated. Flash chromatography on silica gel with methylene chloride/methanol/triethyl amine 98:1:1 gave rac-cis-1-[1-benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-piperazine (9.54 g, 67%) as a yellow oil, MS: m/e=336.3 (M+H+).

Provenance & Evidence