Cefoxitin acid preparation method

Abstract

The invention discloses a cefoxitin acid preparation method, comprising the following steps: adding 7-alpha-methoxyl-3-deacetylcefalotin benzathine salt in acetone at room temperature, cooling the solution and adding chlorosulfonyl isocyanate to react and then producing the finished product by hydrolysis, extraction, decoloration, concentrated crystallization, filtration, dissolution and secondary crystallization. In the invention, acetone with a consumption of 2.6kg / kg which is easy to recycle is used instead of tetrahydrofuran which is used in the prior art with a consumption of 13kg / kg and the production cost is reduced by 120 Yuan / Kg. In the invention water phase decarburization is changed to organic phase decarburization, thus eliminating the step of phase inversion in the original process and avoiding the yield loss in phase inversion process; water phase crystallization is changed to the crystallization method which adopts organic phase for concentrating and adds dichloromethane for crystallizing so that the crystallization is realized fully, the yield is higher and the total yield of cefoxitin is increased from 58% to 67%. The material cost of the cefoxitin acid can be reduced by 240 Yuan / Kg, the total reduced cost can be about 360 Yuan / Kg and the product prepared by the method has stronger market competitiveness and remarkable economic benefit.

Description

technical field [0001] The invention relates to a method for preparing cefoxitin acid by using acetone as a reaction solvent and using 7-alpha-methoxy-3-deacetyl cephalothin benzathine salt as a starting material. Background technique [0002] At present, in the production process of cefoxitin acid at home and abroad, the preparation of cefoxitin acid with 7-α-methoxy-3-deacetyl cephalothin benzine salt as raw material all uses tetrahydrofuran as solvent, and the primary crystallization is all aqueous phase crystallization . Its specific process route is as follows: figure 1 As shown, the steps are as follows: [0003] 1. Chlorosulphonylation: add 7-α-methoxy-3-deacetyl cephalothin benzathine salt to tetrahydrofuran at room temperature, add chlorosulfonyl isocyanate after cooling to -50~-60°C, and control the temperature during the process At -60 to -30°C, when the initial raw material 7-α-methoxy-3-deacetyl cephalothin benzathine salt≤1.0%, the reaction is complete. [...

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Problems solved by technology

[0014] ① Due to the use of tetrahydrofuran as a solvent in the chlorosulfonylation process, although the reaction can be carried out smoothly, it is difficult to recover tetrahydrofuran, and the recovered tetrahydrofuran cannot be reused, resulting in the cost of cefoxitin acid being as high as 2210 yuan / Kg, It is 120 yuan / Kg higher than the cost of using acetone as a solvent

[0015] ②One-time decolorization is water phase decolorization. Before decolorization, there needs to be a phase inversion, that is, the reaction product is transferred from the ethyl acetate phase to the water phase. Due to the existence of the phase inversion in this step, the final product yield is reduced.

[0016] ③Since the primary crystallization is water-phase crystallization, a small amount of ethyl acetate needs to be added to adjust the crystal form during the crystallization process, resulting in incomplete crystallization, which also affects the product yield

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