Preparation of cephamycine intermediate compound

Abstract

The invention relates to a cephamycines intermediate compound formula (I) and a method for making the free acid of the same. According to the formula (I), X1 represents halogen atom C1 or Br, and L<+> represents counter ion which is formed into salt in the presence of alkali and solvent. The method does not need an extremely low temperature and column purification, and has relatively simple operation and ideal product purity; therefore, the method is easy to use in industrial scale. The cephamycines intermediate compound made by the method can be widely used to make cephamycines antibiotics such as cefminox, cefmetazole and cefotetan and so on.

Description

technical field The invention relates to a new preparation method of a compound of formula (I), a key intermediate of cephamycin. Background of the invention Cephamycins refer to cephalosporins with a trans-methoxy group at the C7 position of the β-lactam ring. The presence of methoxy prevents the approach of the lactam ring and the enzyme molecule, enhances the stability of the drug against β-lactamase, and improves the activity against anaerobic bacteria, making this class of antibiotics more resistant to β-lactamase It has strong antibacterial effect on some bacteria producing β-lactamase. The difficulty in the synthesis of cephamycin mainly lies in the introduction of the methoxyl group at the 7α position. In the 1970s and 1980s, this difficulty has attracted widespread attention, and a variety of synthetic routes have been studied, among which the more representative ones are: 1) Acylimine Process: In the presence of a strong base, 7β-amide cephalosporin or 6β-amid...

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Problems solved by technology

But as far as we know, the general methods with industrialized production value at present or the use of particularly unstable and explosive tert-butyl hypochlorite at extremely low temperatures such as -78 ° C or even -90 ° C, etc., the actual production is still very difficult. It is very difficult; or it is necessary to first protect the 4-position carboxyl group into an ester such as diphenylmethyl ester, and then use aluminum trichloride / anisole to remove the 4-position protecting group after introducing the 7α-position methoxyl group. The steps are cumbersome , a large yield loss

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