Process for preparing 3-deacetylate-7-aminocephalosporanic acid

Abstract

The invention discloses a process for preparing 3-deacetylate-7-aminocephalosporanic acid, belonging to the technical field of medicines. The method disclosed by the invention comprises the following steps of: directly catalyzing 3-deacetylate cephalosporin C extract with cephalosporin acylase, then acidifying and crystallizing, washing and drying to obtain solid 3-deacetylate-7-aminocephalosporanic acid. The method only requires one-step normal temperature cracking reaction and one crystallizing process, process rout is short, pollution is less, mole yield of product is more than 86%, and the method disclosed by the invention is applicable to industrialization production.

Description

technical field [0001] The invention relates to a preparation process of a pharmaceutical intermediate, in particular to a preparation process of 3-deacetyl-7-aminocephalosporanic acid, which belongs to the technical field of medicine. Background technique [0002] 3-deacetyl-7-aminocephalosporanic acid is called D-7-ACA for short. Because the amino group at the 7th position and the hydroxyl group at the 3rd position are relatively active, different side chains can be introduced to synthesize a series of cephalosporin antibiotics, such as cephalosporin Cefuroxime, Cefuroxime, Cefpirome, Cefcapene Proxetil, Cefdinir, Ceftazidime, etc. With the increase in the amount of cephalosporin antibiotics and the development of new cephalosporin antibiotics, the demand for D-7-ACA in pharmaceutical production is also increasing. [0003] At present, there are three main methods for preparing D-7-ACA: chemical method, chemical-biological enzymatic method and biological enzymatic method,...

AI Technical Summary

Problems solved by technology

[0004] Among the above-mentioned preparation methods, the chemical method and the chemical-biological enzymatic method have a long process route, and all have to undergo three crystallization processes of cephalosporin C sodium salt (or zinc salt), 7-ACA, and D-7-ACA. Due to the crystallization process, product loss Many, resulting in low yield of the method

In addition, the cracking used in the chemical method requires high temperature, high pressure and low cooling, and the organic solvents used in the reaction materials, such as dichloromethane, aniline, and chlorosilane, are poisonous and harmful pollutants, and a large amount of strong acid and alkali are used. The production of D-7-ACA has to bear heavy energy consumption costs and pollution control costs

In the chemical and biological enzymatic method, 7-ACA is first prepared by enzymatic method, and then chemically or enzymatically cleaved to obtain D-7-ACA. Due to the enzymatic cleavage of 7-ACA, the crystalline product is sticky and difficult to centrifuge during crystallization. And drying problems, need to add solvent to assist crystallization, and need to use a lot of separation equipment, resulting in increased energy consumption and labor costs

The existing biological enzymatic method uses a two-step enzymatic cleavage process, which is cumbersome to operate

And the oxidative cleavage process of D-amino acid oxidase requires a lot of pure oxygen and power consumption, which increases labor and operating costs

[0005] 3-Deacetyl cephalosporin C is an impurity produced during the production of cephalosporin C. In the current industrial production, it is usually separated from cephalosporin C and discarded, which not only consumes a lot of energy, but also increases production costs. and cause serious pollution to the environment