Piperazine → HCID 22141345, compound

Participants

Reaction Steps

Or Method B: (i) To a stirred solution of 6-methyl-6-(3-nitrophenyl)-3-(3-phenylpropyl)azabicyclo[3.1.0]hexane-2,4-dione (Preparation 136, 15.0 g, 41.2 mmol) in tetrahydrofuran (60 ml) under nitrogen was added sodium borohydride (3.27 g, 86.4 mmol) and the reaction mixture was stirred at room temperature for 1 h. The reaction mixture was cooled to between 0° C. and 5° C. and borontrifluoride diethyletherate (16.36 g, 115 mmol) was added. The reaction mixture was allowed to warm to room temperature over 2 h before being heated under reflux for a further 2 h. The reaction mixture was cooled to between 0° C. and 5° C. and an aqueous solution of piperazine (20.92 g in 120 ml) was added. The reaction mixture was then heated under reflux for 18 h. The tetrahydrofuran was removed by distillation and the reaction mixture was allowed to cool to 50° C. Ethyl acetate (90 ml) was added and the resulting biphasic mixture was allowed to cool to room temperature. The phases were separated and the organic extract was washed water (3×60 ml) to afford a solution of 6-(3-nitrophenyl)-6-methyl-3-(3-phenylpropyl)azabicyclo[3.1.0]hexane in ethyl acetate. (ii) To the reaction mixture was added 5% palladium on charcoal (Johnsson Matthey type 87, 1.5 g) and the reaction mixture was placed under an atmosphere of hydrogen (60 psi) at 25° C. for 16 h. The catalyst was removed by filtration through Celite™ and the filtrate was concentrated in vacuo to afford the title compound as a yellow oil which crystallised on standing (11.09 g, 88%).

Provenance & Evidence