反应详情

(1-Methylpiperidin-4-yl)methyl 4-nitrophenyl carbonate (Intermediate 1; 5.70 g, 19.4 mmol) was dissolved in DMF (40 mL). DIPEA (6.75 mL, 38.7 mmol) and 1-phenyl-piperazine (2.96 mL, 19.4 mmol) were added. The reaction mixture was stirred at room temperature for 6 h and then concentrated in vacuo. The residue was dissolved in EtOAc (300 mL) and washed sequentially with sat aq NaHCO3 solution (6×200 mL), brine (50 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 98:1:1 mixture of DCM:MeOH:DIPEA) followed by reverse phase chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-80%) to give (1-methylpiperidin-4-yl)methyl 4-phenylpiperazine-1-carboxylate formate (0.63 g, 10.3%) as a viscous yellow oil.

1. concentrationconcentrated in vacuo
2. dissolutionThe residue was dissolved in EtOAc (300 mL)
3. washwashed sequentially with sat aq NaHCO3 solution (6×200 mL), brine (50 mL)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated in vacuo
6. customThe residue was purified by normal phase column chromatography (
7. washeluting with DCM
8. additionfollowed by a 98:1:1 mixture of DCM
9. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-80%)