Study On The Synthetic Process Of Methoxyamine Hydrochloride

Methoxyamine hydrochloride is an important intermediate for the synthesis of kresoxim-methyl and cefuroxime. Cefuroxime belongs to the second generation semi-synthesis cephalosporins, and it is widely used in industry for its potent antibiotic activity with broad spectrum and resistance to beta lactamase. The need for kresoxim-methyl and cefuroxime is increased in recent years, so the production of methoxyamine hydrochloride shows promising market. However, there are many problems such as defective process, serious pollution and high cost in the methoxyamine hydrochloride's production in our country. Therefore, the synthesis of the cephalosporins intermediates has an important practical significance.This research is to define a synthesis technology in industrialization for methoxyamine hydrochloride by appropriate route chosen from so many methods.We improved the scheme through the experiments,also optimized its reaction condition by orthogonal tests. It's determined that the best route and each step of the synthesis posesses the goal of cutting cost,simplifying operation procedure and improving yield by experiment researth.Methoxyamine hydrochloride was synthesized from hydroxylamine hydrochloride, dimethyl sulphate and ethyl acetate. The optimal synthetic conditions of methylation were that the pH of the methylation was 10, the molar ratio of hydroxylamine hydrochloride and dimethyl sulphate was 1.0:1.05, the molar ratio of hydroxylamine hydrochloride and vitriolc was 1.0:0.5, the reaction time was 6 h, and the reactive temperature was 80℃. With reduced dosage of acetic acid, the yield of product was raised obviously, and the total yield was up to 78%,the purity(HPLC)is above 98%.The products are characterized by applying of 1H-NMR.And the molecular formula has been confirmed.Meanwhile,the melting points of the production of methoxyamine hydrochloride are estimated.The stability of these process condition are verified by continuously five lots of proof tests after we optimized process condition for every step. The yield reaches 78%,and the assay of the final product is 98% by HPLC.Thus this improved technology is defined finally for its feasibility of commercial production.