Novel Synthesis Of Monodeuterium Labeled Ractopamine

?-adrenergic agonists are an important part of veterinary drug residues, posing a potential risk for consumer health, especially for asthma or angiocardiopathy. More analytical methods can accurately and efficiently determine veterinary drug residues in livestock products for food safety, in which employing isotopically labeled ractopamine as an internal standard. To date, there were very few procedures described in the literature for the preparation of deuterium labeled ractopamine. Li's group and Lu's group applied a patent for the preparation of d3- and d4-ractopamine.To better resolve series of technical matters of the existing synthesis methods, three routes to prepare ractopamine was designed by retrosynthetic analysis, based on both past routes and multibie aspects, such as economic, operability. Finitely, a promising and practical route started with p-methoxybenzaldehyde, acetone and 2-bromo-4'-methoxyacetophenone is reported in this article.Therefore, a novel synthetic route to stable deuterium labeled ractopamine was disclosed with 6.49% total yield,98.4% chemical purity and 97.7% isotopic abundance. Its structure and the isotope-abundance were confirmed according to 1H-NMR and HRMS. This deuterium labeled ractopamine could be used for the preliminary and qualitative screening of veterinary drug residues and metabolic mechanism study of ractopamine as its metabolic stability.