Study On Synthesis Of 3-piperidinecarboxylic Acid Ethyl Ester

The process of preparing 3-piperidine carboxylic acid ethyl ester (ethyl nipecotate) was studied in this paper. The starting material 3-methylpyridine was oxidized to nicotinic acid by potassium permanganate. Then nicotinic acid was esterified with ethanol to give ethyl nicotinate. Ethyl nicotinate was hydrogenated to ethyl nipecotate. Synthetic conditions of three steps, involving the amount of catalysts and the solvents, were studied . Esterification reaction condition was studied in detail. The influencing factors of esterification were analyzed by orthogonal test. The amount of sulfuric acid was the most important factor in the process. The optimum condition of esterification was the following: nicotinic acid 10 g ( 0.08 mol ), ethyl alcohol 28 mL (0.48 mol), sulfuric acid 6 mL (0.11 mol), temperature 110 ℃, reaction time 9 h. Under appropriate condition, the yield of ethyl nicotinate was 89.26 %. The purity was 99.51 %. The influencing factors of hydrogenation, such as temperature, reaction time, catalyst amount and solvent were also studied. The synthesized products of the hydrogenated ethyl nicotinate were analysed by combined means of programmed temperature-capillary gas chromatography-mass spectrometry. Using Raney Ni as catalyst, the optimum condition was the following: ethyl nicotinate 15 mL ( 0.11 mol ), solvent 150 mL, Raney Ni 3 g, reaction temperature 60 ℃, hydrogen pressure 2 Mpa , reaction time 3 h. The yield of ethyl nipecotate was 98.09 %. The purity was 97.74 %. The process has important industrial application potential.