Preparation method for producing ainothiazoly loximate by utilizing phase transfer technology

Abstract

The invention discloses a preparation method for producing ainothiazoly loximate by utilizing a phase transfer technology. The preparation method comprises the following steps: A, in an aqueous system, adding ethyl acetoacetate and sodium nitrite into a reaction kettle in proportion for reacting to obtain a nitrosation product; B, reacting the product of the ethyl acetoacetate subjected to nitrosation with a saturated aqueous solution of a methylating agent and sodium carbonate in the presence of a phase transfer catalyst by controlling the temperature, separating an aqueous layer after the reaction, and then directly carrying out chlorination; C, controlling the reaction temperature, introducing chlorine gas into the product subjected to the methylation, washing with water, and layering to obtain a chlorination reactant; D, adding thiourea, sodium acetate and phase transfer catalyst tetrabutyl ammonium chloride into the chlorination reactant, controlling the reaction temperature, and centrifugalizing the product; E, adding flake caustic soda and water into a cyclization product, regulating the pH value with hydrochloric acid, and centrifugalizing; and F, adding methyl alcohol into the centrifugalization product for refining, centrifugalizing and drying to obtain the ainothiazoly loximate. The method disclosed by the invention is easy to implement, is simple and convenient to operate, has low production cost, greatly improves the quality and yield of the product, and ensures safe and reliable production processes.

Description

technical field [0001] The present invention relates to the technical field of using phase transfer to carry out methylation reaction, more specifically to a preparation method of using phase transfer to produce aminothiaxamic acid, which is applied to the synthesis of pharmaceutical intermediates and drugs, such as C-alkylation, O-alkylation Chemical production of ether products, synthesis of dl-mandelic acid, etc. The application of this technology can improve product yield, simplify process operation, enhance safety production and other advantages. Background technique [0002] Ammothioxamic acid is an important pharmaceutical intermediate, mainly used in the synthesis of cephalosporin antibiotic preparations, and is the side chain of cefotaxime sodium, ceftriaxine, ceftazidine, etc. This antibiotic preparation is a new type of antibiotic drug with strong antibacterial power developed abroad in the 1970s. At present, the world sales of this class of antibiotics accou...

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Problems solved by technology

[0003] The synthesis process of traditional aminothioxamic acid can be divided into according to different raw materials: methyl acetoacetate method, ethyl acetoacetate method, chloroacetoacetate method; Wherein the ethyl acetoacetate method takes ethyl acetoacetate as raw material through oximation, Etherification, bromination, cyclization, hydrolysis, refining and other steps of preparation; using the traditional process to produce lt-aminothiaxamic acid consumes 2.31 tons of ethyl acetoacetate. This process not only wastes raw materials, but also has dangerous production processes, high production costs, and poor product quality; It is difficult to promote production technology and adapt to the current market competitiveness

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