The synthesis of cefmenoxime hydrochloride and 7-amino-3-methoxy-methyl-3-cephem-4-carboxylic acid (7-AMCA), intermediate of cefpodoxime proxetil are studied in this paper. The synthetic route of cefmenoxime hydrochloride and 7-AMCA from 7-amino-cephalosporanic acid (7-ACA) was designed and successfully established here.The reaction condition were optimized and confirmed.The cefmenoxime hydrochloride was synthesized by two routes using 7-ACA as the raw material.The route which 7-ACT was firstly synthesized from the reaction of MMT and 7-ACA in C3-position of 7-ACA and then reacted with MAEM in C7-position to produce Cefmenoxime (the yield was 86%), was proved to be superior to the route that the C7-position of 7-ACA was firstly transformed before the C3-position (the yield was 69%). It was found that solvent had remarkable effect on the yield and dichloromethane can give the best result. What's more, ultrasound was proved to significantly shorten the reaction time.The intermediate VI was obtained by protecting amino at C3-position via acylation with phenylacetyl chloride using 7-ACA as the raw material and then reacted with methanol at C7-position catalyzed by CaCl2 to get a methoxyl intermediate. Finally, the 7-AMCA was synthesized by cleavage of the protective group with a total yield of 24%.7-AMCA can also be synthesized by reaction of intermediateâ…¥with methyl iodide catalyzed by the potassiumt tert-butanolate and followed by the cleavage of the protective group. The overall yield of this route was 32%. Another synthetic pathway was developed usingâ…¥, which was obtained by the protection of amino and carboxylic group at C4 and C7 position, as the raw material.The derivateâ…¥first reacted with methanol using a silver nitrate catalyst and then cleaved the protective group to obtain the 7-AMCA.The over yield of this route was 51%.
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