Sodium Hydroxide → HCID 54449804, compound

Participants

Reaction Steps

Lithium aluminum hydride (0.378 g) was added to an ice-cooled suspension of (3R)-1-benzyl-3-(3-methoxy-4-methylphenyl)-2,5-piperazinedione (1.35 g) in tetrahydrofuran (22 ml) below 5° C. under nitrogen atmosphere. The mixture was stirred under reflux for 3 hours. After the mixture was cooled below 5° C., 2N sodium hydroxide was added to the mixture. After the mixture was stirred for 30 minutes, the insoluble materials were removed by filtration and washed with tetrahydrofuran. The filtrate and the washing were combined and evaporated under reduced pressure to give (3R)-1-benzyl-3-(3-methoxy-4-methylphenyl)piperazine as an oil. A solution of 3,5-bis(trifluoromethyl)benzoyl chloride (0.80 ml) in dichloromethane (1 ml) was added dropwise over 5 minutes to an ice-cooled solution of (3R)-1-benzyl-3-(3-methoxy-4-methylphenyl)piperazine obtained by above procedure and triethylamine (0.84 ml) in dichloromethane (10 ml) below 5° C. After being stirred for 30 minutes at the same temperature, the reaction mixture was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using mixed solvents of hexane and ethyl acetate (4:1). The fractions containing the objective compound were collected and evaporated under reduced pressure to give (2R)-4-benzyl-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3-methoxy-4-methylbenzyl)piperazine (1.92 g) as an oil.

Provenance & Evidence