Synthesis Of Intermediates To β-lactam Antibiotics

β-lactam antibiotics is a kind of antibiotics containingβ-lactam-based structure. They have great significance in clinical application due to their strong antibacterial effect.In recent years,because the widespread use of antibiotics has raised the drug resistance of bacteria,it is urgent to develop the synthesis of new antibiotics.This paper is focused on the synthesis of methyl 2-(benzamidomethyl) -3-oxobutanoate,the main intermediate during the synthesis ofβ-lactam,which is an important intermediate in the synthsis ofβ-lactam antibiotics.A new synthetic route was developed:starting from benzamide,via hydroxymethanation,halogen nucleophilic substitution,and C-alkylation to get methyl 2-(benzamidomethyl) -3-oxobutanoate.By analyzing the structures and properties of the products and the by-products in each step,the possible factors that influence the side reactions were discussed.Furthermore,the experimental conditions were optimized.The yields of the three-step reaction were 90.4%,84.3%,and 60.5%,respectively.This paper has discussed a new method to synthesize the intermediate for the further reactions to giveβ-lactam and its derivatives.This route shows great industrial value since it is environmentally friendly,low-cost and user-friendly.