反应详情

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)+.

1. customafter 90 min volatile material was removed by rotary evaporation
2. customthe mixture obtained
3. concentrationconcentrated in vacuo
4. custommixture was partitioned between water and ethyl acetate
5. washThe organic layer was washed with brine
6. dry with materialdried (MgSO4)
7. customevaporated