Hydrochloric Acid → 4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-1-[3-((R)-2-hydroxymethyl-pyrrolidin-1-yl)-propyl]-piperazin-2-one

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Reaction Steps

Hydrogen chloride solution (4 M in 1,4-dioxane, 2 ml) was added to a solution of 4-[3-((R)-2-hydroxymethyl-pyrrolidin-1-yl)-propyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (intermediate 7; 157 mg, 0.46 mmol) in 1,4-dioxane (2 ml), then after 90 min volatile material was removed by rotary evaporation. The residue was taken up in dichloromethane (10 ml), treated with 4-methylmorpholine (232 mg, 2.30 mmol), and the mixture obtained concentrated in vacuo. The residue was taken up in N,N-dimethylformamide (2 ml), then 4-methylmorpholine (232 mg, 2.30 mmol), 3,4-dichlorocinnamic acid (108 mg, 0.48 mmol), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluoro-phosphate (262 mg, 0.69 mmol) were added. The solution was stirred at room temperature for 3 h, then mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried (MgSO4), and evaporated. Chromatography (SiO2; CH2Cl2/MeOH/NH4OH 80:20:0.25) produced the title compound (82 mg, 41%). Colorless gum, MS (ISP)=440.3 (M+H)+.

Provenance & Evidence