反应详情

温度

0 °C

1-(3-Hydroxypropyl)-4-piperazine (0.63 g, 4.0 mmol) was dissolved in DCM (30 mL) and cooled to 0° C. DIPEA (1.39 mL, 8.0 mmol) and p-nitrophenyl chloroformate (0.80 g, 4.0 mmol) were added. The reaction mixture was stirred at room temperature for 2 hours and then phenylpiperazine (0.61 mL, 4.0 mmol) was added. The reaction mixture was stirred at room temperature for 16 hours and then concentrated in vacuo. The residue was dissolved in EtOAc (100 mL) and washed sequentially with 1M aq Na2CO3 solution (4×100 mL), and concentrated in vacuo. The residue was purified by reverse phase chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-30%). The resulting residue was dissolved in DCM (30 mL) and stirred with solid Na2CO3 for 20 minutes, filtered and concentrated in vacuo. The resulting residue was purified by reverse phase HPLC (gradient eluting with acetonitrile in water, 5-45%) to give 3-(4-methyl-piperazin-1-yl)propyl 4-phenylpiperazine-1-carboxylate (148 mg, 11%) as a colourless oil.

1. stirringThe reaction mixture was stirred at room temperature for 16 hours
2. concentrationconcentrated in vacuo
3. dissolutionThe residue was dissolved in EtOAc (100 mL)
4. washwashed sequentially with 1M aq Na2CO3 solution (4×100 mL)
5. concentrationconcentrated in vacuo
6. customThe residue was purified by reverse phase chromatography (gradient
7. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-30%)
8. dissolutionThe resulting residue was dissolved in DCM (30 mL)
9. stirringstirred with solid Na2CO3 for 20 minutes
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe resulting residue was purified by reverse phase HPLC (gradient eluting with acetonitrile in water, 5-45%)