Preparation method of cefoxitin sodium

Abstract

The invention discloses a preparation method of cefoxitin sodium. The preparation method comprises the following steps: (1) bromizing, for example, the site 7 of a main nucleus of cefalotin by using an NBS (N-bromosuccinimide) reagent to form a bromination compound; performing nucleophilic substitution at the site 5 by using a methoxyl group to generate an intermediate IV; (2) performing acyl group hydrolysis on the site 3 of the intermediate IV to obtain an intermediate V; (3) substituting hydrogen atoms on the hydroxyl group by using chloriosulfonyl isocyanate, and then hydrolyzing to obtain the cefoxitin sodium. The method has the advantages of simple process, high product yield, high purity and high reaction selectivity; no special equipment is used in the production; the preparation method is suitable for industrial production.

Description

technical field [0001] The invention relates to the field of raw material medicine preparation, in particular to a preparation method of cefoxitin sodium. Background technique [0002] Cefoxitin sodium, chemical name: (6R,7S)-3-carbamoyloxymethyl-7-methoxy-8-oxo-7-[2(2-thiophene, acetamido)]- 5-Thia-1-azabicyclo-[4,2,0]-oct-2-ene-carboxylic acid sodium salt, molecular formula: C 16 h 16 N 3 NaO 7 S 2 , molecular weight: 449.43, the chemical structure is as follows: [0003] [0004] Cefoxitin Sodium, developed by Merk Company of the United States and listed in 1994, is a new type of antibiotic produced by semi-synthesis of methoxycephalosporin C produced by Streptomyces. Cefoxitin sodium can kill bacteria due to its ability to inhibit the synthesis of bacterial cell walls, and due to its structural specificity, it is stable to the β-lactamase produced by bacteria, so it has huge market potential. [0005] At present, the synthetic method of cefoxitin sodium has man...

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Problems solved by technology

There are three main synthetic routes: (1) Using cephamycin as a raw material, first modify the amino group on its carboxylic acid side chain, and then modify its four-membered ring. This route has cumbersome processes and requires precious metal catalysts and other shortcomings, so it has not met the needs of large-scale industrial production; (2) Using cephalosporin acid or sodium salt as raw material, first modify the C of 7-aminocephalosporanic acid (7-ACA) 3 The side chain on the position, and then modify the C 7 Amino side chain or ceftinic acid or sodium salt as raw material, first modify the C of 7-ACA 7 Amino side chain, then modify C 3 Although the raw material of this route is cheap and easy to get, molecular sieves need to be used in the reaction process and the reaction steps are generally long, so it has not been able to industrialized production; (3) with methoxycephalosporin (7- MAC) as the raw material, first modify the C of 7-MAC 7 amino side chain, and then modify the side chain on the C3 position. Although the synthesis steps of this route are relatively simple, 7-MAC is expensive and not easy to obtain, so it has not been applied to industrial production.

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