Diisopropylethylamine → (1-Methylpiperidin-4-yl)methyl 4-(3-methylphenyl)piperazine-1-carboxylate

関与物質

反応手順

(1-Methylpiperidin-4-yl)methyl 4-nitrophenyl carbonate (Intermediate 1; 4.30 g, 14.6 mmol) was dissolved in DMF (50 mL). DIPEA (8.91 mL, 51.1 mmol) and 4-(3-methylphenyl)piperazine dihydrochloride (3.64 g, 14.6 mmol) were added. The reaction mixture was stirred at room temperature for 4 hours and then concentrated in vacuo. The residue was dissolved in EtOAc (500 mL) and then washed sequentially with 1 M aq NaOH solution (6×200 mL), brine (50 mL), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in DCM (150 mL) and methyl isocyanate resin (1.0 g) was added and the reaction mixture shaken for 14 h, filtered and then 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-methylpiperidin-4-yl)methyl 4-(3-methylphenyl)piperazine-1-carboxylate (0.65 g, 13.3%) as a pale yellow oil.

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