Synthesis
The general procedure for the synthesis of tert-butyl 4-(iodomethyl)piperidine-1-carboxylate from N-BOC-4-piperidinemethanol was as follows: tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate (2.25 g, 10.5 mmol, 1.0 eq.), imidazole (858 mg, 12.6 mmol, 1.2 eq.) and triphenylphosphine (3.30 g, 12.6 mmol. 1.2 equiv) were dissolved in anhydrous THF (30 mL) and cooled to 0 °C. Anhydrous THF solution of iodine (3.20 g, 12.6 mmol, 1.2 eq.) was slowly added dropwise with stirring. After the dropwise addition, the reaction mixture was stirred at room temperature for 14 hours. After completion of the reaction, the reaction was quenched with saturated Na2S2O3 solution. The aqueous layer was extracted with EtOAc, the organic layers were combined, washed with water, dried over anhydrous MgSO4 and concentrated under reduced pressure. The crude product was diluted several times with cold ether and filtered to remove the white crystals. The filtrate was concentrated under reduced pressure to afford the target compound tert-butyl 4-(iodomethyl)piperidine-1-carboxylate as a colorless oil in 92% yield. The product was analyzed by 1H NMR, 13C NMR and IR spectroscopy to confirm that the data were consistent with the literature reports.
References
[1] Journal of Medicinal Chemistry, 1994, vol. 37, # 17, p. 2721 - 2734
[2] European Journal of Medicinal Chemistry, 2019, p. 234 - 248
[3] Organic and Biomolecular Chemistry, 2014, vol. 12, # 5, p. 783 - 794
[4] Patent: WO2007/30366, 2007, A1. Location in patent: Page/Page column 231-232
[5] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 9, p. 2233 - 2239
