Method for continuously synthesizing ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate

Abstract

The invention discloses a method for continuously synthesizing ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate, and belongs to the field of cephalosporin medicine synthesis. According to the method, a continuous reaction device is utilized, 4-chloro-2-methoxyimino ethyl acetoacetate reaction liquid and a thiourea solution are added into a reactor according to a certain proportion, a certain temperature is kept, a soda ash solution is used for adjusting the pH value, the reaction liquid overflows to a cooler to be cooled, a product is obtained after filtering and washing, the liquid phasepurity is larger than 99.5%, and the yield is 85%-93%. The method has the advantages that the synthesis of ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate realizes continuous reaction, the variable control in the reaction process is more efficient and timely, the product quality stability is obviously improved, and meanwhile, as the continuous reaction is realized, the heat in the reaction process is effectively controlled, the energy can be effectively saved, the production cost is reduced, and the method is suitable for industrial large-scale production.

Description

technical field [0001] The invention belongs to the field of medicine synthesis, and relates to the synthesis technology of ethyl aminothiaxate, in particular to a method for continuously synthesizing ethyl aminothiaxate. Background technique [0002] Ethyl aminothioxamate, the chemical name is (Z)-2-(2-amino-4-thiazole)-2-methoxyiminoacetic acid ethyl ester, which is an important raw material for the synthesis of cephalosporin aminothioxamic acid. The curative effect is dozens of times that of penicillin and has little toxic and side effects on the human body. [0003] At present, the production process of ethyl acetoacetate generally uses ethyl acetoacetate as a raw material, and is prepared through oximation, alkylation, distillation, halogenation, and cyclization. However, there are still many problems in the traditional route and process, such as synthesis Often operation is complicated in the technology, automation level is low, and yield fluctuates greatly, product q...

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Problems solved by technology

[0003] At present, the production process of ethyl acetoacetate generally uses ethyl acetoacetate as raw material, and is prepared through oximation, alkylation, distillation, halogenation, and cyclization. However, there are still many problems in the traditional route and process, such as synthesis Often operation is complicated in the technology, automation level is low, and yield fluctuates greatly, product quality is not stable etc. shortcoming; In addition, reducing production cost is the main problem that industrial production faces; Optimization, but most of them are researches on synthetic processes, few involve engineering technology optimization

[0004] Liu Zhenqiang [CN106632137A preparation method of ethyl thiourea] has reported a method for preparing ethyl thiourea in the same reactor, but the cyclization reaction is still adding the halogenated compound dropwise to the thiourea solution, which still belongs to the category of intermittent operation. Wang Meng [CN104478825A Synthetic method of aminothiaxamic acid] proposed a synthetic method of aminothiaxamic acid, wherein the cyclization reaction uses sodium acetate as a buffer salt, but the cost of sodium acetate is relatively high, and it increases the difficulty of wastewater treatment

In addition, the raw materials used in these two methods are all brominated compounds, which have high cost in industrial production.

[0005] Zhao Qi [CN107857741A The new synthesis process of aminothiaxamic acid] proposed a new synthesis process of aminothiaxamic acid, involving the synthetic method of ethyl aminothiaxamic acid as 4-chloro-2-methoxyimine-ethyl acetoacetate and sodium carbonate solution were dropped into Thiourea solution, this reaction adopts chlorides as raw materials, but the amount of thiourea added is relatively large, and tetramethylammonium bromide is added as a phase transfer catalyst to increase mass transfer, resulting in a large amount of organic matter in the wastewater, increasing the waste water Handling Difficulty

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