Recation Method Study On Decarboxylative Cross-Coupling To Synthesise Aryl Acetic Acids And Derivatives

Aryl acetic acids and derivatives are a kind of common pharmaceuticalintermediates, and have also been widely used in the daily chemical and food. Thetraditional synthesis method of aryl acetic acids and derivatives throughesterification of acid and alcohol is very simple, but the raw material of aryl aceticacids are obtained by hydrolysis reaction of aryl cyanide or aryl amide, and thereaction conditions are relatively harsh. Another method is arylation of diethylmalonate, acetate or acetyl acetate. The base of the reaction must be addedequivalent, and some even need to add vast quantities of alkali, which limited thescope of the substrate. So we hope to develop a new synthesis method of aryl aceticacids and derivatives, in order to overcome the weakness of traditional synthesismethods.The main content of this paper are:(1) The target products will be obtained bydecarboxylative cross-coupling of potassium malonate monoesters and derivatives withbenzene halide.(2) The proposed mechanism of the reaction is inferred on the basis of thefront experimental data and relevant literature.(3) This new strategy for decarboxylativecross-coupling of potassium3-ethoxy-2-methyl-3-oxopropanoate with2-bromo-6-methoxynaphthalene is used to synthesize naproxen, which is ananti-inflammatory and antipyretic analgesic drug.An efficient catalytic protocol for Pd-catalyzed decarboxylative cross-couplingof potassium malonate monoesters and derivatives with aryl bromides and chloridesare described. Because of its mild reaction condition, high activity,stereoselectivity and regioselectivity, this new reaction proceeded by extruding CO2provides an alternative method for the preparation of diverse aryl acetic acids andderivatives.