Study On The Synthetic Process Of Loratadine

Allergic disease is a common disease,and its pathogenesis is related to a chemical mediator in the human body-histamine and histamine receptors.Loratadine,as a second-generation classic anti-allergic drug,can antagonize the binding of histamine and its H1 receptor.Because of its high receptor selectivity,good curative effect,and low side effects,it has become the first-line drug for the treatment of allergic diseases in clinical practice.In addition,Loratadine is also an important pharmaceutical and chemical intermediate for the synthesis of the third-generation antihistamines Desloratadine and Rupatadine.The structural characteristics,structure-activity relationships and clinical advantages of loratadine were briefly described in this article,the currently reported synthetic routes of loratadine were systematically analyzed,and after a comprehensive comparison of existing synthetic researches,a synthetic route was determined and its process was optimized in this paper.In this thesis,2-cyano-3-methylpyridine is used as the starting material,and it undergoes Ritter reaction under acidic conditions,and then undergoes alkylation reaction under the catalysis of alkali,and then undergoes phosphorus oxychloride deprotection and Grignard reaction,cyclization reaction,and ethyl chloroformate substitution reaction,to obtain loratadine.The feed ratio of raw materials and reaction conditions such as reaction temperature,catalyst and other factors was systematically investigated and their influence on the total yield of the target compound were explored.The crystallization method of the Ritter reaction product was changed,and the post-treatment process was innovated too;in the cyclization reaction step,The production costs was reduced by use of a cheap and low-toxic cyclization system,reaction conditions were improved,and the formation of by-products were effectively inhibited.A simple,green and economic synthesis route for loratadine was obtained,with a total yield of 31%,which is suitable for scale-up production.