The Synthesis Of Key Intermediate Of Saxagliptin And Palladium Catalyzed α-Oxocarboxylic Acid Decarboxylative Acylation

2-(1-adamantyl)2-oxoacetic acid is one of the key chemical intermediates of saxagliptin which is used for treating type 2 diabetes.We summarized the literatures and optimized a preferred route.And we make research of Pd-catalyzed decarboxylative C-C cross-coupling reaction employing α-carbonyl carboxylic acid.In the first chapter,we briefly described saxagliptin and summaried the synthesis method of 2-(1-adamantyl)2-oxoacetic acid by different starting materials.In the second chapter,we optimized a route using adamantane carboxylic acid as a starting material to synthesize 2-(1-adamantyl)-oxoacetic.We get 2-(1-adamantyl)-oxoacetic a total yield of 64.5%,through chlorination reaction,substitution reaction,hydrolysis reaction and oxidation reaction and every step of the reaction has been optimized.This reaction route has the advantage of short reaction steps,simple operation,less environmental pollution and high yield.In the third chapter,we described the transition-metal-catalyzed coupling reactions and mainly reviewed decarboxylation coupling reaction employing α-carbonyl carboxylic acid and summarized catalyst system and reaction mechanism.In the fourth chapter,we designed decarboxylation coupling reaction using 4-morpholino-N-phenyl amide as substrate.We have successfully developed urea groups as a guide group participation in C-H activation acylation and work out a suitable catalytic system for the substrate.Under the optimized reaction system we make expension of the substrate and carried out the yield between 30.8%~61.1%.