Methyl iodide → HCID 68556175, compound

Participants

Reaction Conditions

Reaction Steps

A 50-mL 2-neck round bottom flask was fitted with a nitrogen inlet and rubber septum and charged with N,N-diisopropylamine (0.598 mL, 4.26 mmol) in anhydrous THF (15 mL). The solution was cooled to −70° C., treated with n-butyllithium (3.05 mL, 4.26 mmol) and stirred for 30 min. A solution of methyl 1-(4-chloro-3-methoxyphenyl)piperidine-4-carboxylate (1.10 g, 3.88 mmol) in THF (3 mL) was added dropwise to the reaction and the resulting mixture was stirred at −70° C. for 1 h. After this time, the mixture was treated with iodomethane (0.253 mL, 4.07 mmol) and slowly warmed to RT. TLC and LC-MS (m/z=298.21) indicated the reaction was complete. The mixture was treated with water (25 mL) and extracted with EtOAc (3×30 mL). The extract was dried (Na2SO4) and concentrated on a rotary evaporator to give methyl 1-(4-chloro-3-methoxyphenyl)-4-methylpiperidine-4-carboxylate (1.06 g, 3.56 mmol, 92% yield) as a yellow solid. 1H-NMR (400 MHz, CDCl3) δ ppm 7.17 (1 H, d, J=8.56 Hz), 6.48 (1 H, s), 6.44 (1 H, dd, J=8.69, 2.14 Hz), 3.86 (3 H, s), 3.70 (3 H, s), 3.38 (2 H, ddd, J=12.72, 4.03, 3.90 Hz), 2.82-2.91 (2 H, m), 2.19-2.26 (2 H, m), 1.52-1.64 (2 H, m), 1.24 (3 H, s).

Provenance & Evidence