Step A: At -78°C, a solution of n-BuLi (1.05 equivalents) in THF was added dropwise to a solution of bromobenzene (1.0 equivalents) in anhydrous THF. After addition, the mixture was stirred at -78°C for about 0.5 hours. Then, a solution of Boc-4-piperidinone in THF was added dropwise via syringe at -78°C. After addition, the resulting mixture was stirred at -78°C under N2 for 2 hours, and then heated to rt. The reaction mixture was quenched with saturated NH4Cl solution, and the resulting mixture was extracted with EtOAc (50 mL, 30 mL). The combined organic phases were washed with brine, dried over anhydrous Na2SO4, and concentrated under vacuum. The residue was purified by column chromatography (PE/EtOAc) to give the compound 1-BOC-4-phenyl-4-hydroxypiperidin. Step B: Add a solution of HCl (3 equivalents) in dioxane to a solution of compound 1-BOC-4-HYDROXY-4-PHENYLPIPERIDINE (1 equivalent). Stir the reaction mixture at room temperature for approximately 2 hours, at which point no Sm is detected by LCMS. Concentrate the reaction mixture to obtain the desired product, 4-HYDROXY-4-PHENYLPIPERIDINE.
