1-Benzyl-4-hydroxyMethylpiperidin-4-ol

109105-86-4

92197-36-9

A3a) Synthesis of 1-benzyl-4-(hydroxymethyl)piperidin-4-ol: 200 g of AD-Mix-Alpha (Aldrich, Art. No. 39,275-8) was dissolved in a mixed solvent of 500 mL of water and 300 mL of tert-butanol, and stirred for 20 hours. The reaction mixture was cooled to 0 °C and 13.7 g (144 mmol) of methanesulfonamide and 27.0 g (144 mmol) of 1-benzyl-4-methylene piperidine were added sequentially. After removing the cooling bath, stirring was continued at room temperature for 22 hours. To the reaction mixture was added 59 g of Na2SO3 and stirred at room temperature for 1 hour. Subsequently, 2 L of EtOAc and 500 mL of saturated NaHCO3 solution were added and the organic phase was separated and dried over Na2SO4. After removing the desiccant and solvent, the residue was dissolved in 150 mL EtOAc and filtered through an alumina (Alox) column. The filtrate was discarded and the product was eluted from the Alox column with 1 L of MeOH. After evaporation of the solvent, the resulting product was used for subsequent reactions without further purification. Yield: 26.0 g (82% yield).ESI-MS: (M + H)+ = 222.HPLC retention time (Method B): 1.4 min.