The Study On The Synthesis Of Duloxetine Hydrochloride

Duloxetine hydrochloride is an effective third generation antidepressant.As a dual inhibitor of serotonin/norepinephrine reuptake,it can inhibit the serotonin and norepinepHine reuptake effectively,and improve the concentration of the intercellular space of the brain.In addition,the product has a good therapeutic effect on female stress urinary incontinence and diabetic peripheral nerve pain.Clinical application has the characteristics of quick effect and good tolerability,safety,less side effects and so on.This thesis is divided into three parts:In the first part,the international and domestic situation of depression and the research status of antidepressants were reviewed.Various synthetic methods of duloxetine are also introduced.In the second part,we introduces a synthetic route to duloxetine hydrochloride salt from 2-acetyl thiophene,paraformaldehyde,a methylamine hydrochloride by condensation,reduction,split,etherification.Compared with the traditional process,the route of synthesis of duloxetine hydrochloride reduces the demethylation steps,the cost and environmental pollution.At the same time the etherification reaction conditions were optimized: sodium hydride was replaced by sodium tert-butoxide,which avoid partial racemization of intermediates during etherification it would help us to get qualified duloxetine hydrochloride without the resolution of tartaric acid.In the third part,the stability of the process was verified by the optimized production process.The experimental data showed that the yield of process was stable and had the potential of industrial production.