General procedure for the synthesis of N-Boc-3-iodomethylpiperidine from tert-butyl 3-(hydroxymethyl)piperidine-1-carboxylate: Imidazole (1.58 g, 23.2 mmol), triphenylphosphine (6.09 g, 23.2 mmol), and iodine (4.72 g, 18.6 mmol) were sequentially added to a solution containing 1-(tert-butoxycarbonyl)piperidin-3-ylmethanol (2.00 g, 9.29 mmol) in a solution of benzene (50 mL). The reaction mixture was stirred at room temperature for 3 hours. Upon completion of the reaction, the mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure. Water was added to the residue and subsequently extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent ratio: hexane/ethyl acetate = 20:1 → 5:1) to afford 2.91 g (96% yield) of the target compound N-Boc-3-iodomethylpiperidine as a light yellow oil. The product was confirmed by 1H NMR (400 MHz, CDCl3): δ 1.19-1.28 (1H, m), 1.40-1.52 (10H, m), 1.61-1.68 (2H, m), 1.91-1.95 (1H, m), 2.54-2.69 (1H, m), 2.79-2.84 (1H, m), 3.08 (2H , d, J=6.7 Hz), 3.84 (1H, td, J=13.4, 3.7 Hz), 3.97-4.13 (1H, m). Mass spectrometry analysis (FAB+) showed the molecular ion peak m/z: 326 ([M+H]+).
