4-AMINO-1-BENZYL-PIPERIDINE-4-CARBOXYLIC ACID

28936-94-9

39143-25-4

The general procedure for the synthesis of 1-benzyl-4-amino-4-piperidinecarboxylic acid using 8-benzyl-2,4-dioxo-1,3,8-triazaspiro[4,5]decane as a starting material was as follows: 2.4 kg of sodium hydroxide was dissolved in 10 L of deionized water in a 20 L reactor. Subsequently, 614 g of 8-benzyl-1,3,8-triazaspiro[4.5]decane-2,4-dione (1.38) was added to this solution to form a reaction suspension. The suspension was heated to 80°C. After reaching 80°C, the temperature was gradually increased at a rate of 10°C per step. When the temperature was raised to 105°C, the reaction mixture began to foam vigorously. The reaction was maintained at 108°C with continuous stirring overnight. Upon completion of the reaction, the mixture was cooled to 10 °C, and 5 L of concentrated hydrochloric acid was slowly added dropwise to adjust the pH to 7-8. During the dropwise addition, the reaction temperature was controlled to be no more than 23 °C. A solid was precipitated from the reaction solution and the precipitate was collected by filtration. The resulting solid was dried under vacuum at 40 °C for 3 days, followed by drying at 80 °C overnight to give 469.7 g of 1-benzyl-4-amino-4-piperidinecarboxylic acid (I.39) in a final yield of 85% of the theoretical value.