Phenylacetic Acid → 4-Hydroxy-4-(1-carboxy-1-phenyl-methyl)piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

To a solution of phenylacetic acid (13.7 g, 0.100 mol) in THF (90 mL) at 0° C. was slowly added iPrMgCl (2M in Et2O, 100 mL, 0.200 mol). The mixture was stirred at rt for 1 h and then N-Boc-4-piperidone (20.0 g, 0.100 mol) was added as a solid. Stirring was continued for 1 h and then the mixture was quenched with sat. NH4Cl and acidified to pH 2 using concentrated HCl. The mixture was extracted with EtOAc (×3) and the combined organic layers were dried over Na2SO4, filtered and concentrated to give the title compound (33.3 g, 99%) as a colorless foam which was of sufficient purity to continue to the next step:

Provenance & Evidence