161491-24-3

79099-07-3

616-38-6

161491-24-3

60% sodium hydride (3.5 g, 88 mmol) was suspended in anhydrous toluene (50 mL) at room temperature and protected by nitrogen. Dimethyl carbonate (4.32 g, 48.0 mmol) was added slowly and dropwise to this suspension over a period of 0.5 hours. After the addition of a few drops of methanol, a solution of N-tert-butoxycarbonyl-4-piperidone (4.8 g, 24 mmol) dissolved in anhydrous toluene (20 mL) was added dropwise to the reaction mixture while maintaining the reaction system at 80 °C with stirring. The reaction mixture was continued to be stirred at the same temperature for 3 h. The reaction mixture was subsequently cooled to 0 °C (ice bath) and the pH was adjusted to 6-6.5 with acetic acid. the resulting cold mixture was diluted with water (10 mL) and the pH was adjusted to 8 with 5% sodium hydroxide solution. the toluene layer was separated and the aqueous layer was extracted with toluene (20 mL). The combined organic layers were dried with anhydrous sodium sulfate and concentrated under reduced pressure. The product was dried under vacuum to afford methyl methyl-1-tert-butoxycarbonyl-4-oxo-3-piperidinecarboxylate (5.0 g, 80% yield). The resulting compound did not require further purification and could be used directly in the subsequent reaction.