Oxalyl chloride → 5-{[4-(2-tert-Butylphenyl)piperazin-1-yl]carbonyl}-1-phenylpyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To an ice-cold stirred solution of 5-oxo-1-phenylproline (Reference Example 12, 0.22 g, 1.08 mmol) and N,N-dimethylformamide (3 drops) in tetrahydrofuran (10 mL) was added oxalyl chloride (0.14 g, 1.10 mmol). The mixture was stirred at 0° C. for 30 min, and then allowed to warm to room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in pyridine (10 mL). To this mixture was added 1-(2-tert-butylphenyl)piperazine dihydrochloride (Reference Example 1, 0.30 g, 1.03 mmol) and the mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between ethyl acetate and 10% NaHCO3 solution. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting solid was dissolved in ethyl acetate and filtered through a pad of silica gel. The filtrate was concentrated under reduced pressure to give an orange solid. This solid was recrystallized from hexane-ethyl acetate to give the title compound (0.26 g, 59%) as a light yellow solid.

Provenance & Evidence