Methyl iodide → Tert-butyl 3-benzoyl-3-methylpiperidine-1-carboxylate

Participants

Reaction Steps

A stirred solution of (R)-tert-butyl 3-benzoylpiperidine-1-carboxylate (409 mg, 1.42 mmol) in dry THF (15 mL) under N2 was cooled to −78° C. A solution of lithium bis(trimethylsilylamide) in THF (2.84 mL of 1.0M, 2.84 mmol, 2 equiv) was added dropwise. After 30 min, a solution of iodomethane (220 μL, 3.5 mmol, 2.5 equiv) in DMPU (512 μL, 4.24 mmol, 3.0 equiv) was added slowly. After 15 min, the reaction mixture was allowed to warm to rt and stirred overnight. LC-MS showed the reaction was complete. Brine (50 mL) was added to quench the reaction. The organic layer was separated and the aqueous layer was extracted with EtOAc (2×75 mL). The combined organic layers were dried over Na2SO4. After concentration, the crude product was purified by chromatography on a prepacked 12-g silica gel cartridge eluted with a 0-35% EtOAc in hexanes gradient to afford tert-butyl 3-benzoyl-3-methylpiperidine-1-carboxylate (278 mg, 65%). LC-MS (3 min) tR=1.92 min, m/z 326 (M+Na).

Provenance & Evidence