Sodium hydride → 2-(1-Methylpiperidin-4-yl)ethyl 4-(4-methylphenyl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

NaH (60% dispersion in mineral-oil, 0.81 g, 42.2 mmol) was suspended in heptane (10 mL) under an argon atmosphere. The heptane was decanted off, and the flask was charged with THF (20 mL) and cooled to 0° C. A solution of 2-(1-methyl-piperidin-4-yl)-ethanol (1.01 g, 7.03 mmol) in THF (20 mL) was added drop-wise, followed by a solution of 4-nitrophenyl 4-(4-methylphenyl)piperazine-1-carboxylate (2.89 g, 8.46 mmol) in THF (20 mL). The reaction mixture was allowed to warm to room temperature and stirred for 48 hours. The reaction mixture was then cooled to 0° C. and quenched with the drop-wise addition of sat aq NaHCO3 solution and concentrated in vacuo. The residue was dissolved in EtOAc (200 mL), washed with a NaHCO3 solution (4×50 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 90:10 mixture of DCM:MeOH) followed by reverse phase chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-20%). The resulting residue was dissolved in DCM (50 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give the title compound 2-(1-methylpiperidin-4-yl)ethyl 4-(4-methylphenyl)piperazine-1-carboxylate (0.21 g, 7%) as a cream solid.

Provenance & Evidence