| Dapoxetine hydrochloride is a new selective serotonin re-uptake inhibitors(SSRIs), it was used to treat emotional obstacles originally, but was widely recognized because of its significant efficacy in the treatment of premature ejaculation. The clinical trial on dapoxetine show the significant efficacy, tolerability, fewer side effects and safety of treatment of premature ejaculation. Dapoxetine has broad market prospects.In this thesis, each of the synthetic method of dapoxetine were evaluated in detail. Based on the literature, a new synthetic route for industrial manufacture of dapoxetine was designed for improving the disadvantages of existing processes. The main processing method was as follows: benzaldehyde, ammonium acetate and malonic acid as raw materials, through Knoevenagel condensation reaction, Na BH4-I2 reaction, Eschweiler-Clarke methylation, Williamson ether synthesis. S-dapoxetine were resolved by D-(-)-tartaric acid. The total yield synthetic process is 14.8 %(bezaldehyde as original material). The intermediate products were characterized by NMR and the target product dapoxetine was characterized by NMR and MS. The conditions of the synthesis process of each step was studied including ratio of materials, reaction Time and solvent.In the article, dapoxtine’s quality standard was basically determined after careful research on the relative material limit and effective ingredient contents. Specific research of dapoxetine includes the following aspects: character, appearance, solubility, melting point, acidity etc. The content of the dapoxetine hydrochloride raw material is greater than 99.0%, each impurity is less than 0.1%, the total content of impurities are less than 0.5%, the optical purity of dapoxetine is 99.9%.The synthetic process in this thesis is simple and easy to operate, has mild processing conditions, cheaper raw materials, the preliminary quality of dapoxetine is established and is suitable for industrial production of dapoxetine hydrochloride. |
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