Synthesis Of 1-Carbethoxy-2-Methyl-4-Piperidone

Piperidine derivatives, as an important kind of heterocyclic nitrogen intermediate, are applied widely in the production of medicines, pesticides and fine-chemicals. Piperidones are very important compounds especially in the manufacture of medicines. Some domestic chemical workers have done research on the synthesis of piperidine derivatives recently. Derived from diesters they synthesized 1-substituted-4 -piperidones, such as 1-methyl-4-piperidone, 1-propyl-4-piperidone, 1-benzyl-4 -piperidone.1-Carbethoxy-2-methyl-4-piperidone was selected as the target molecular of this paper, and it would be synthesized derived from a kind of diester. Differing from the synthesis of 1-substituted-4-piperidones, the diester needed for the target is a secondary amino asymmetric diester. So less research had been done on the synthesis of this particular diester, that we met more difficulties and done more work on this.Through esterification, two steps of addition, two steps of condensation and hydrolysis-decarboxylation, altogether six-step reactions, 1-carbethoxy-2-methyl-4- piperidone has been synthesized from ammonia, crotonic acid, ethyl acrylate and ethyl chloroformate. The overall yield was up to 32%.Nine different compounds were synthesized and identified through 1H NMR, MS or IR. One of the compounds, ethyl N-(2,2′-dicarbethoxydiethyl)-β-aminobutyrate (EDCEAB) was unknown, and it has been identified through 1H NMR and MS.Some achievement has been obtained on the synthesis of ethyl N- (2-carbethoxyethyl)-β-aminobutyrate(ECEAB), in this paper. Ethylβ-aminobutyrate (EABA) was synthezied derived from ammonia and ethyl crotonate, yield up to 78.4%; ECEAB was synthezied derived from EABA and ethyl acrylate, yield up to 75.1%. These two yields are both higher than reported in the literature. It has been the first time to do experiment on ammonia and methyl acrylate at -20℃, furthermore 3,3′,3′′-nitrilo-tri-propionic acid trimethyl ester(NTPTM) was got in the yield of 30.9%.The successful synthesis of the target compound has provided a potential methodology for large-scale industrial production. At the same time, it also provides consultable reference for the synthesis of other piperidine derivatives.