Synthesis method of (3R, 4R)-3-[(R)-1-tertiary butyl dimethyl Si-O-ethyl]-4-acetoxyl-2-azetidinone derivative

Abstract

The invention relates to a synthesis method of a (3R, 4R)-3-[(R)-1-tertiary butyl dimethyl Si-O-ethyl]-4-acetoxyl-2-azetidinone derivative. The derivative is prepared by carrying out a reflux reaction on 4-AA at 30-120 DEG C in an organic solvent by using zinc powder as a catalyst. Compared with the traditional beta-lactam antibiotic derivative using a larger group, the invention has the advantages that a smaller group easier to obtain is used for synthesizing the beta-lactam antibiotic derivative in the method, and the synthesis method has high activity, good selectivity and high atom economy. Raw materials used in the reaction have low toxicity and are easy to obtain, and a heavy metal catalyst is not needed to be used, which is safe and has no influence on subsequent pharmaceutical synthesis. The method has simple process, easy operation and moderate reaction condition.

Description

technical field The present invention relates to a method for synthesizing heterocyclic pharmaceutical intermediates, in particular to a key intermediate for the synthesis of lactam antibiotics—(3R,4R)-3-[(R)-1-tert-butyldimethyl Synthetic method of siloxyethyl]-4-acetoxy-2-azetidinone derivatives. Background technique β-lactam antibiotics are a class of antibiotics discovered recently. These antibiotics can selectively bind to the penicillin-binding protein (PBP) on the bacterial membrane, so that it cannot be cross-linked, resulting in a defect in the cell wall, resulting in bacterial cell rupture. And die. The toxicity of β-lactam antibiotics to human cells is very low, and such antibiotics have no effect on human cells within their effective antibacterial concentrations. It has ultra-broad-spectrum, long half-life, high-efficiency antibacterial activity and pharmacokinetic properties. Among them, the most representative drugs are carbapenem antibiotics. β-lactam ant...

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Problems solved by technology

The reported derivatives of carbapenem antibiotics are mainly concentrated on large groups like 4-BMA, and there are basically no corresponding reports on some relatively small groups like methyl bromoacetate

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