Formic Acid → (1-Methylpiperidin-4-yl)methyl 4-(4-chlorophenyl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

(1-piperidin-4-yl)methyl 4-(4-chlorophenyl)piperazine-1-carboxylate (4.07 g, 12.0 mmol) was dissolved in formic acid (20 mL) and 35% aqueous formaldehyde solution (20 mL). The reaction mixture was heated at 95° C. for 90 minutes, and then cooled to room temperature. The reaction mixture was quenched by slowly pouring it onto 1M aq Na2CO3 solution (200 mL), basified to pH10 with 1M aq KOH solution (30 mL) and extracted with DCM (3×100 mL). The combined organic layers were washed with brine (50 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 97:2:1 mixture of DCM:MeOH:DIPEA) followed by reverse phase column chromatography (gradient eluting with MeOH in water, 0-80%) to give (1-methylpiperidin-4-yl)methyl 4-(4-chlorophenyl)piperazine-1-carboxylate (1.30 g, 30.7%) as a white solid.

Provenance & Evidence