The Research Of The Synthesis Of Roxithromycin And Clarithromycin

The thesis focused on the research and development of Roxithromycin and Clarithromycin preparation process.The Synthesis of Roxithromycin:Our synthetic route is started from Erythromycin thiocyanate, through oximation reaction, then oxime etherification with 2-methoxyethoxymethyl chloride we synthesized by ourselves, the target compound-Roxithromycin were obtained. The total yield is 42.3%. The purity reached 99%. Through MS, IR, NMR we confirms the synthesis of Roxithromycin. The process improvement is that sodium methoxide was displaced by its methyl alcohol solution. The better yield and purity were obtained.The Synthesis of Clarithromycin:Our synthetic route is started from Erythromycin thiocyanate, through oximation reaction, etherification, silylation, selective methylation, deprotection and reduction to get the target compound Clarithromycin. The total yield is 42.3%. The purity reached 99%. The main three impurities were also synthesized. Through MS, IR, NMR we confirms the intermediate, impurities, and final product. The reaction conditions were optimized and the process improvements are as follows:1. Use methyl bromide to displace traditional iodomethane, lower cost was obtained.2. Use toluene and DMSO to displace traditional THF and DMSO, the post-processing and retrieve are easier.3. In the deprotection reaction, use acetic acid to displace formic acid, because of its weaker acid, the side-reaction is under control, the product quality is better.