The preparation method of nifuratel

Abstract

The invention belongs to the technical field of synthesis of medicines and particularly relates to a nifuratel preparation method. The nifuratel preparation method comprises the following steps: taking epoxy propyl dimethyl sulfide as the starting material, having a ring-opening reaction with tert-butyl carbazate to obtain N'-(2-hydroxyl-3-methylmercapto-propyl)-tert-butyl carbazate; having a ringclosing reaction with urea under the catalytic action of cuprous bromide, obtaining a key intermediate N-(Boc-amino)-5-methylmercapto-methyl-2-oxazolidinone; hydrolyzing 5-nitro furfural diacetate under the action of trifluoroacetic acid to obtain 5-nitrofurfural, condensing with N-(Boc-amino)-5-methylmercapto-methyl-2-oxazolidinone, and obtaining nifuratel. In the process route, the cheap easy-to-get agents are chose, the operation difficulty and the processing burden caused after the reaction are reduced, the environmental harm is reduced, the production safety is guaranteed, and the preparation method is an easy, green and economical process route for the preparation of the nifuratel.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, and in particular relates to a preparation method of nifuratel. Background technique [0002] 5-[(methylthio)methyl]-3-{[(5-nitro-2-furan)methylene]amino}-2-oxazolidinone, Chinese name: Nifuratel, English name : Nifutatel is a drug mainly used for gynecological infections developed and produced by Italy Puli Chemical Company. The drug is a broad-spectrum antibiotic, especially for common pathogens of gynecological infections such as Gram-positive and It has a strong killing effect on worms, molds, chlamydia and mycoplasma, and has a good curative effect on the treatment of common gynecological vaginal infections caused by trichomonas, candida albicans, and bacteria. It is now on the market in my country and many other countries with dosage forms such as tablets, capsules, and suppositories. [0003] The chemical structure of Nifuratel is as follows: [0004] [0005] The publicly rep...

AI Technical Summary

Problems solved by technology

[0013] (1) The separation process of compound 3 and compound 4 mostly adopts high-vacuum distillation, which requires high equipment, difficult operation, and low yield. Because the used methyl mercaptan and sodium methyl mercaptide have stench, it is easy to cause The destruction of the environment has a greater pressure on environmental protection;

[0014] (2) In the process of preparing oxazolidinone, when compound 5 is synthesized from compound 4, sodium methoxide / methanol system is used, and sodium metal is also used, which has great potential safety hazards, and it is very easy to cause combustion and explosion. Feed and production operations

[0019] (1) the toxicity of dimethyl sulfate is bigger, causes the operational difficulty of technique to become bigger;

[0020] (2) Although sodium metal is not used in the cyclization reaction, the danger of sodium hydride is also very large, and it is very easy to spontaneously ignite and explode;

[0021] (3) The separation process of compound 4 and compound 5 requires vacuum distillation, which requires high equipment

[0022] In addition, it is found by research that in the prior art, 5-nitrofurfural diethyl ester is generally used in 10% H 2 SO 4 Or under the condition of Lewis acid, it is heated to a higher temperature and hydrolyzed to prepare 5-nitrofurfural. Because 5-nitrofurfural is easy to change color when it sees light, and the aldehyde group is unstable, it will cause faster discoloration under heating conditions, and the side reaction is relatively fast. Many, easy to generate polymers, poor product quality; meanwhile, the yield of 5-nitrofurfural decreases, resulting in poor quality of nifuratel, deepened color, and reduced yield

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