Flomoxef process impurity and preparation method thereof

Abstract

The invention discloses a flomoxef process impurity and a preparation method of the flomoxef process impurity. The method comprises the following steps: synthesizing an intermediate (6R, 6R, 6R, 6R) from flomoxef sodium; the preparation method comprises the following steps: synthesizing a target impurity intermediate from starting materials including (3R, 7R)-3-(chloromethyl)-7-amino-7-methoxy-8-oxo-5-oxa-1-azabicyclo [4.2. 0] octyl-2-ene-2-carboxylic acid benzhydryl ester, methylthioacetic acid and methylthioacetic acid, and condensing the target impurity intermediate with a side chain 1-hydroxyethyl-5-mercapto-1H-tetrazole sodium salt to obtain the target impurity. Finally, removing a benzhydryl protecting group from titanium tetrachloride to obtain (6R, 7R)-7-(2-methylthio) acetamido)-3-(((1-(2-ethoxyl)-1H-tetrazole-5-yl) sulfur) methyl)-7-methoxy-8-oxo-5-oxa-1-azabicyclo [4.2. 0] oct-2-ene-2-formic acid; according to the invention, convenience is provided for quality research of flomoxef sodium bulk drugs and preparations, and a detection method and a judgment basis are provided for production and safe medication of flomoxef sodium.

Description

technical field [0001] The invention belongs to the technical field of medicines, and in particular relates to the main impurity structure of fluoxefom sodium, an axocefem antibiotic, and a preparation method thereof. Background technique [0002] Fluoxefor sodium, chemical name: (6R,7R)-7-(2-((difluoromethyl)thio)acetamido)-3-(((1-(2-hydroxyethyl)-1H- Sodium tetrazol-5-yl)thio)methyl)-7-methoxy-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, as Oxycephem antibiotics, developed by Shionogi Co., Ltd. of Japan, were first listed in Japan in 1998 as injectable Oxycephem antibiotics under the trade name Flumarin. Fluoxefor sodium has a broad antibacterial spectrum, strong antibacterial ability, and is stable against β-lactamase, and has a better curative effect on clinically refractory and multiple infections. [0003] The chemical structural formula is: [0004] [0005] Regarding the related impurities of fluoxefom sodium, there are few reports in the literature....

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Problems solved by technology

[0016] 3. In addition, there are many steps in the synthesis process of fluoxetal sodium, the stability of the intermediate is poor, and various impurities are easily generated during the process, most of which are sold in the market, and the structure is as follows:

[0019] With the in-depth research on the synthesis process and product quality of fluoxefom sodium, the present invention has discovered a process impurity in the raw material drug of fluoxefom sodium, and carried out directional synthesis and structural confirmation. There is no relevant patent report for this impurity at present

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