Method for synthesizing ceftiofur intermediate and ceftiofur

Abstract

The invention belongs to the technical field of chemical synthesis, and concretely relates to a method for synthesizing a cefotaxime intermediate 7-amino-3-[(2-furyl-carbonyl)-thiomethyl]-3-cephem-4-carboxylic acid and ceftiofur. The method comprises the following steps: sequentially adding 7-aminocephalosporanic acid, thiofurancarboxylic acid, a solid base catalyst gamma-Al2O2-O2<2->Na<+>, zeolite and water into a reaction kettle, performing stirring and reacting at room temperature for 1.5-2.5 h, filtering the obtained reaction solution, adjusting the pH value of the obtained filtrate to 5.5-6.5 by using an appropriate amount of hydrochloric acid, filtering the filtrate, washing the obtained filter cake with water to obtain a white solid, and performing vacuum drying to obtain the 7-amino-3-[(2-furyl-carbonyl)-thiomethyl]-3-cephem-4-carboxylic acid. The method uses water as a solvent, so the production cost is reduced, the produced products have a high yield and a high purity, and the promotion of industrial production is benefited.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a ceftiofur intermediate and a synthesis method of ceftiofur. Background technique [0002] The chemical formula of ceftiofur: C 19 h 17 N 5 o 7 S 3 , chemical name: (6R,7R)-7-[2-(2-aminothiazol-4-yl)-(Z)-2-(methoxyimino)acetamido]-3-[(2- Furanylcarbonyl)thiomethyl]-3-cephem-4-carboxylic acid, its structural formula is: [0003] . [0004] Ceftiofur (Ceftiofur) is the first third-generation cephalosporin antibiotic specially used in animals, successfully developed by Pharmacia&Upjohn. Because of its strong antibacterial activity, excellent pharmacokinetic characteristics, small toxic and side effects, and low residue, it is widely used in the treatment of bacterial diseases such as cattle, sheep, pigs, dogs, and chickens all over the world. Ceftiofur is a prodrug for the production of ceftiofur hydrochloride or ceftiofur sodium, and it can also be...

AI Technical Summary

Problems solved by technology

In this method, 7-aminocephalosporanic acid reacts with furan-2-carbonyl mercaptan under the catalysis of boron trifluoride etherate, and the intermediate is obtained through alkali treatment. The yield of this method is high, but boron trifluoride etherate And boron trifluoride gas catalysis is difficult to operate in industrial production, and has a relatively high risk, because boron trifluoride is suffocating, it will be hydrolyzed immediately when it encounters moisture in the air, and highly toxic fluoride fumes will be generated when it decomposes. Therefore, the safety requirements for operators are extremely high.