Step A: Synthesis of methyl 4-oxo-1-(phenylmethyl)-3-piperidinecarboxylate hydrochloride. A solution was prepared by dissolving 1-benzyl-4-piperidone (56.5 kg, 1.0 eq.) in toluene (189 L) at 15 °C to 25 °C. In another reactor, toluene (659L), potassium tert-butoxide (71.9 kg, 2.25 eq.) and dimethyl carbonate (51.5 kg, 2.0 eq.) were added at 15 °C to 25 °C to form a slurry. The slurry was heated to 80°C to 90°C. A toluene solution of 1-benzyl-4-piperidone was slowly added to the slurry over a period of 60 to 90 minutes. After 90 minutes of reaction, the mixture was cooled to below 15°C. The reaction was quenched with acetic acid (38.5 kg, 2.25 eq.) and water (367 L). The two phases were separated and the organic layer was filtered to remove solids. The organic filtrate was concentrated by distillation under reduced pressure to about 150 L. Toluene (799 L) was added to the concentrate and hydrogen chloride gas (11.0 kg, 1.05 eq.) was passed through to form a hydrochloride precipitate. The slurry was stirred at 10°C to 15°C for 30 minutes. The solid was collected by filtration, washed with hexane (~130 L) and dried under vacuum to give 79.4 kg of methyl 4-oxo-1-(phenylmethyl)-3-piperidinecarboxylate hydrochloride in 97.8% yield. Elemental analysis (C14H17NO3-HCl) Calculated values: C 59.3, H 6.39, N 4.94; measured values: C 59.7, H 6.65, N 4.85.
