GENERAL STEPS: N-tert-butoxycarbonyl-4-piperidone (5 g, 25 mmol) was dissolved in tetrahydrofuran (100 mL) and the resulting solution was cooled to 0 °C. Under cooling conditions, sodium hydride (60% dispersed in mineral oil, 2.10 g, 53 mmol) was added all at once and the resulting turbid mixture was stirred for 10 minutes. Subsequently, iodomethane was added slowly and the reaction mixture was gradually warmed up to room temperature with continuous stirring overnight (12 hours). Upon completion of the reaction, the light orange colored mixture was concentrated under reduced pressure. The concentrated residue was extracted by partitioning with ether and water. The aqueous phase was back-extracted with ether and all organic phases were combined, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated to give a light yellow solid. The solid was ground with a hexane solution of 4% ethyl acetate (50 mL) to afford 1-Boc-2,2-dimethylpiperidin-4-one as a cream-colored solid (1.8 g, 32% yield). The product was characterized by 1H-NMR (CDCl3, 300 MHz): δ 3.73 (t, 2H), 3.43 (br s, 2H), 2.49 (t, 2H), 1.49 (s, 9H), 1.13 (s, 6H).
