4-Methylmorpholine → [1-(2-Methoxyethyl)piperidin-4-yl]-methyl 4-(4-methylphenyl)piperazine-1-carboxylate

関与物質

反応条件

反応手順

(1-(2-methoxyethyl)piperidin-4-yl)methanol (Intermediate 3, step 2; 1.73 g, 10.0 mmol) was dissolved in DCM (50 mL) and cooled to 0° C. NMM (1.21 mL, 11.0 mmol) and 4-nitrophenyl chloroformate (2.02 g, 10.0 mmol) were added. The reaction mixture was stirred at 0° C. for 15 minutes and then added to a solution of 4-(4-methylphenyl)piperazine dihydrochloride (2.62 g, 10.5 mmol) and DIPEA (6.10 mL, 35.0 mmol) in DMF (75 mL). The reaction mixture was stirred at room temperature for 4 h and then concentrated in vacuo. The residue was dissolved in EtOAc (300 mL) and then washed sequentially with 1M aq NaOH solution (6×100 mL), brine (100 mL), and then dried (MgSO4) 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 (70 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give [1-(2-methoxyethyl)piperidin-4-yl]-methyl 4-(4-methylphenyl)piperazine-1-carboxylate (0.95 g, 25.4%) as a pale yellow oil.

情報源と証拠