Dimethyl Sulfoxide → (S)-1-(3-Benzyloxy-propyl)-3-methyl-piperazin-2-one

Participants

Reaction Steps

Dimethyl sulfoxide (7.60 g, 97.2 mmol) was added dropwise at −78° C. to a solution of oxalyl chloride (6.17 g, 48.6 mmol) in dichloromethane (300 ml) then after 10 min a solution of {(S)-1-[(3-benzyloxy-propyl)-(2-hydroxy-ethyl)-carbamoyl]-ethyl}-carbamic acid tert-butyl ester (16.8 g, 44.2 mmol) in dichloromethane (300 ml) was added at a temperature below −70° C. After 1 h, triethylamine (16.1 g, 159 mmol) was added, then after 15 min the ice bath was removed. The reaction mixture was allowed to reach room temperature, then washed with sat. aq. sodium hydrogencarbonate solution and brine, dried (MgSO4), filtered, and evaporated. The residue was taken up in dichloromethane (300 ml), then triethylsilane (10.3 g, 88.4 mmol) and trifluoroacetic acid (75.6 g, 663 mmol) were added at room temperature. The reaction mixture was stirred at room temperature for 16 h, then evaporated. The residue was dissolved in dichloromethane (100 ml), then triethylamine (60 ml) was added at 0° C. over 30 min, then after 45 min the reaction mixture was concentrated. The residue was dissolved in ethyl acetate and water, then 2 M aq. sodium carbonate solution was added under ice cooling. The organic layer was separated, washed with brine, dried (MgSO4), filtered, and evaporated. Chromatography (SiO2; dichloromethane/methanol/25% aq. ammonia solution 90:10:0.25) produced the title compound (9.07 g, 78%). Colorless oil, MS (ISP)=263.4 (M+H)+.

Provenance & Evidence