Methyl iodide → 1-Benzyl 3-ethyl 3-methylpiperidine-1,3-dicarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-benzyl 3-ethyl piperidine-1,3-dicarboxylate (2.107 g, 7.23 mmol) in dry THF (22 mL) and DMPU (1.4 mL, 1160 mmol) cooled at −78° C. was added dropwise lithium bis(trimethylsilyl)amide (1.271 g, 7.59 mmol, 7.60 mL of 1M solution in THF). After addition, the reaction mixture was stirred at −60° C. for 1 h. Then iodomethane (0.520 mL, 8.32 mmol) in DMPU (0.344 mL, 2.86 mmol was added dropwise. After addition, the reaction was stirred at −60° C. for 1.5 h, then slowly warmed up to −20° C. over approximately 1 hr. The reaction was quenched by the addition of saturated aqueous NH4Cl. The reaction solution was extracted with EtOAc (2×). The combined organics were washed with saturated aqueous NH4Cl and saturated aqueous NaCl. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-30% EtOAc/Hex. The desired fractions were concentrated to give product, benzyl 3-ethyl 3-methylpiperidine-1,3-dicarboxylate (1.66 gm, 5.44 mmol, 75.2% yield) as a light brown oil. Anal. Calcd. for C17H23NO4 m/z 305.3, found: 306.2 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.44-7.27 (m, 5 H), 5.20-5.09 (m, 2 H), 4.24-4.04 (m, 2 H), 3.99 (d, J=13.19 Hz, 1 H), 3.59 (br. s., 1 H), 3.27 (d, J=7.15 Hz, 1 H), 3.13 (d, J=12.64 Hz, 1 H), 2.16-1.95 (m, 1 H), 1.74-1.52 (m, 2 H), 1.51-1.39 (m, 1 H), 1.25-1.07 (m, 6 H).

Provenance & Evidence