Method for preparing 2 beta-methyl penicillanate benzhydryl dioxide

Abstract

The invention provides a method for preparing a 2 beta-methyl penicillanate benzhydryl dioxide, which is to prepare the 2 beta-methyl penicillanate benzhydryl dioxide by four-step reactions. In the method, hydrobromic acid and sodium nitrite or cupric bromide serving as a brominating agent and other methods are adopted, especially bromide is generated by using adsorption of anionic resin, and water is a side product, so that the method is safe and environmentally friendly; the resin can be used repeatedly; the reaction molar yield can be remarkably improved, reaching over 75 percent; and dichloromethane, water, little glacial acetic acid, particularly as well as a catalytic amount of concentrated sulfuric acid are used to replace massive glacial acetic acid serving as a solvent, so that massive glacial acetic acid is removed. The method has unique process, stable product quality, mild process condition and easy control, the traditional azidation reaction and ethynylation reaction are eliminated, the production cost is reduced, the environmental pollution is greatly reduced, and no special equipment is required. The method is suitable for industrial generation in scale.

Description

technical field [0001] The invention relates to a preparation method of 2β-triazolemethyl penicillanic acid benzyl dioxide. Background technique [0002] 2β-triazolemethyl penicillanic acid diphenylmethyl ester dioxide as described below is one of the main intermediates for the synthesis of a novel β-lactamase inhibitor-tazobactam. [0003] Tazobactam is a broad-spectrum and high-efficiency β-lactamase inhibitor developed by Japan Greenhouse Pharmaceutical Company. Promising β-lactamase inhibitors, but due to their long synthesis steps and complex synthesis techniques, they are still a hot spot in drug synthesis research. [0004] 2β-triazolemethyl penicillanic acid diphenylmethyl ester dioxide is one of the most critical intermediates in the synthesis of tazobactam. The following structural formula, because the yield of this step reaction has been very low, so its improvement There is a lot of space. At present, there are many studies on it at home and abroad. The tradit...

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Problems solved by technology

[0003] Tazobactam is a broad-spectrum and high-efficiency β-lactamase inhibitor developed by Japan Greenhouse Pharmaceutical Company. Promising β-lactamase inhibitors, but due to its long synthesis steps and complex synthesis techniques, it is still a hot spot in drug synthesis research

[0004] 2β-triazolemethyl penicillanic acid diphenylmethyl ester dioxide is one of the most critical intermediates in the synthesis of tazobactam. The following structural formula, because the yield of this step reaction has been very low, so its improvement a lot of space

Its disadvantages: the raw material 1-trimethylsilyl-1,2,3-triazole is difficult to synthesize, the yield is low, and explosion may occur during the synthesis process, and the target product needs to be passed through the column. The above conditions limit it. mass production of

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