General procedure for the synthesis of N-CBZ-4-piperidinemethanol (1-CBZ-4-hydroxymethylpiperidine) from 4-(hydroxymethyl)piperidine and benzyl chloroformate: 4-(hydroxymethyl)piperidine (2.0 g, 17.4 mmol) was dissolved in anhydrous dichloromethane (DCM, 100 mL), and the solution was cooled to 0 °C and stirred. Triethylamine (4.8 mL, 34.8 mmol) and benzyl chloroformate (3.7 mL, 34.8 mmol) were added sequentially, then the reaction mixture was slowly warmed to room temperature and stirring was continued for 2 hours. Upon completion of the reaction, the mixture was transferred to a partition funnel and layered with DCM (50 mL) and water (30 mL). The organic phase was separated and the aqueous phase was extracted with DCM (2 x 50 mL). All organic phases were combined, washed once with brine (30 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified by column chromatography using a gradient elution with hexane/EtOAc (70% to 100%) to afford 3.85 g (89% yield) of N-benzyloxycarbonyl-4-(hydroxymethyl)piperidine (E-12) as a clear oil. Its 1H NMR (CDCl3) data were as follows: δ 1.17 (m, 2H), 1.72 (m, 3H), 2.15 (br s, 1H), 2.78 (t, 2H, J = 12 Hz), 3.47 (d, 2H, J = 6.04 Hz), 4.20 (d, 2H, J = 11.68 Hz), 5.12 (s, 2H), 7.33 (m , 5H).
