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

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

(1-piperidin-4-yl)methyl 4-(4-methylphenyl)piperazine-1-carboxylate (Example 3; 9.75 g, 30.7 mmol) was dissolved in formic acid (3 mL), 35% aqueous formaldehyde solution (3 mL) and water (20 mL). The reaction mixture was heated at 95° C. for 45 minutes, and then cooled to room temperature. The reaction mixture was quenched by slowly pouring it onto 1M aq Na2CO3 solution (400 mL) and extracted with EtOAc (4×150 mL). The combined organic layers were washed with brine (75 mL), dried (MgSO4) and concentrated in vacuo. The residue was recrystallised from heptane and then purified by reverse phase column 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. The residue was recrystallised from heptane to give (1-methylpiperidin-4-yl)methyl 4-(4-methylphenyl)-piperazine-1-carboxylate (4.38 g, 43.0%) as a white solid.

Herkunft & Nachweise