Methyl iodide → tert-Butyl 3-methyl-4-oxopiperidine-1-carboxylate

Participants

Reaction Steps

To a solution of tert-butyl 4-oxopiperidine-1-carboxylate (10.0 g, 50.2 mmol) in tetrahydrofuran (50 mL) was added lithium diisopropylamide (2.0 M in THF, 1.5 mL, 3.01 mmol) at −78° C. After 1 h, iodomethane (0.19 mL, 3.01 mmol) was added and the reaction mixture was allowed to warm to ambient temperature over 48 h before being quenched with 1M ammonium chloride and extracted with ethyl acetate. The organic layer was concentrated in vacuo and the residue purified by flash column chromatography (SiO2, 9:1 hexanes/ethyl acetate) to give tert-butyl 3-methyl-4-oxopiperidine-1-carboxylate (4.1 g, 38%) as a yellow solid: 1H NMR (CDCl3, 300 MHz) δ 4.24-4.12 (m, 2H), 3.32-3.20 (m, 1H), 2.94-2.75 (m, 1H), 2.61-2.38 (m, 3H), 1.50 (s, 9H), 1.05 (d, J=6.9 Hz, 3H).

Provenance & Evidence