Ethyl N-Boc-piperidine-4-carboxylate CAS 142851-03-4

functional group transformations

Application Fields

Is there a more environmentally friendly synthetic method to replace this substance

Application of Low Eutectic Solvent (DES):

Low melting point solvents (DES) such as glucose urea low melting point solvents (NADES) are green solvents that replace traditional petrochemical solvents. They are formed by the complexation of Lewis acids or Br ø nsted acids with Lewis bases (usually halide anions), possessing unique physicochemical properties, low cost, low toxicity, biodegradability, and biological activity. These characteristics make NADES potentially applicable in extraction techniques, especially when safety is crucial in solvent selection processes.

Natural low melting point solvent (NADES):

Natural low melting point solvents (NADES) use plant metabolites such as sugars, amino acids, and organic acids as starting materials, and have high extraction efficiency and low toxicity. These solvents can be directly added to food as additives or formulas, and are ideal solvent systems for measuring the extraction efficiency, product purity, and safety of foodborne polysaccharides.

I. Early Background and Raw Material Foundation (Mid-to-Late 20th Century)

Its discovery originated from the research boom of piperidine heterocyclic compounds. From the 1950s to the 1970s, ethyl 4-piperidinecarboxylate, as a core piperidine ester intermediate, had achieved industrial synthesis. It was mainly prepared via esterification and hydrogenation reduction of isonicotinic acid, laying a solid raw material foundation for subsequent protecting group modification. Meanwhile, the Boc protecting group (tert-butoxycarbonyl) was successfully developed in the 1960s. Due to its mild deprotection performance, it became the mainstream choice for amino protection and provided technical support for the selective protection of nitrogen atoms on the piperidine ring.

II. First Synthesis and Structural Confirmation (Late 1990s)

From 1998 to 2002, driven by the vigorous research and development of targeted anti-tumor and neurological drugs, researchers firstly adopted ethyl 4-piperidinecarboxylate as the starting material. Under weakly alkaline conditions with triethylamine as the acid scavenger, the raw material reacted with di-tert-butyl dicarbonate (Boc₂O) in dichloromethane at 0 °C, achieving precise Boc protection of the piperidine nitrogen atom and successfully synthesizing ethyl N-Boc-piperidine-4-carboxylate. The chemical structure was verified by ¹H NMR and mass spectrometry. Its CAS number 142851-03-4 was officially registered between 2002 and 2003, and relevant synthetic patents were publicly disclosed in the same period.

III. Industrialization and Application Expansion (Early 21st Century to Present)

After 2003, surging demand emerged as this compound served as a critical intermediate for multi-target kinase inhibitors such as Vandetanib. The synthetic process was upgraded from laboratory bench scale to large-scale industrial production. Through precise temperature control and strict anhydrous operation, the overall yield was increased to over 95% with a product purity of 99%. In 2007, it was commercially included by major reagent suppliers including Sigma-Aldrich. Gradually, it has become a standard protected piperidine intermediate for pharmaceutical synthesis and heterocyclic construction, establishing its core status in organic synthesis and drug discovery.