4-Piperidinecarboxylic acid, 1-[(4-methoxyphenyl)methyl]-, methyl ester synthesis

Yield:1057277-34-5 67%

Reaction Conditions:

with triethylamine in tetrahydrofuran at 60; for 72 h;

Steps:

4-Methoxybenzyl chloride (1.10 g, 6.98 mmol) was added dropwise to a solution of isonipecotic acid methyl ester (1.00 g, 6.98 mmol) and triethylamine (1.40 g, 14 mmol) in THF (30 ml) and the mixture was stirred at 60° C. for 72 h. 5% strength sodium bicarbonate solution (50 ml) was then added to the reaction mixture and the mixture was extracted with ethyl acetate (3×50 ml). The combined organic phases were dried with sodium sulfate and concentrated i. vac. The residue was purified by flash chromatography with cyclohexane/ethyl acetate (2:1).Yield: 1.23 g (67%) of methyl 1-(4-methoxybenzyl)piperidine-4-carboxylate¹H-NMR (DMSO-d₆): 1.53 (dq, 2H); 1.77 (dd, 2H); 1.93 (dt, 2H); 2.28 (tt, 1H); 2.71 (td, 2H); 3.35 (s, 2H); 3.58 (s, 3H); 3.72 (s, 3H); 6.86 (d, 2H); 7.17 (d, 2H).

References:

US2008/306084,2008,A1 Location in patent:Page/Page column 47