Studies On Synthesis And Quality Of Esomeprazole Magnesium

Esomeprazole is the s-isomer of omeprazole and is the world's first single isomer proton pump inhibitor.It can reduce gastric acid secretion by specifically inhibiting the proton pump of gastric parietal cells,which is suitable for gastroesophageal reflux diseases,and the effect of inhibiting gastric acid is better than omeprazole and other proton pump inhibitors,and has better clinical treatment effect for acid related diseases.Because of the instability of esomeprazole,in the actual production process,the main preparation is esomeprazole sodium or esomeprazole magnesium.In this paper,esomeprazole magnesium was studied,the main research areas are as follows.The synthesis process of esomeprazole magnesium is as follows: using2-mercapto-5-methoxybenzimidazole and 2-chloromethyl-3,5-dimethyl-4-methoxypy ridine hydrochloride as starting materials,the intermediate omeprazole sulfide was obtained through etherification reaction.Then,the asymmetric oxidation of omeprazole sulfide was carried out with toluene as the solvent,D-(-)-tartaric acid diethyl ester,tetraisopropyl titanate and N,N-ethyldiisopropylamine as the chiral auxiliary reagent,cumene hydroperoxide as the oxidant,and esomeprazole was obtained,and finally through salt forming reaction,the product could reach relevant quality standards without further purification.At the same time,based on the content and yield of the target product,the reaction conditions in the reaction process were compared and screened,and the optimal synthesis route was obtained.Study on the quality of esomeprazole magnesium: the structure of the intermediate and esomeprazole magnesium was characterized by IR and NMR.The properties of esomeprazole magnesium were investigated from its appearance,water content and weight loss on drying,and the related substances and optical isomers of the product were determined by HPLC.The content of magnesium was determined by atomic absorption spectrophotometer.The innovation of this paper: in view of the current situation that the traditional synthesis route of esomeprazole is complex,the yield is low and the purification of product is difficult,the main purpose of this paper is to optimize the synthesis process,focusing on the asymmetric oxidation reaction in the preparation process of esomeprazole.The experimental conditions are mild,the process operation is simple,the yield is good,and the product purity is high synthesis route.