Method for preparing intermediate for carbapenem antibiotics

Abstract

The invention discloses a method for preparing an intermediate for carbapenem antibiotics. The method comprises the following steps: dropwise adding 1-2 moles of large steric hindrance organic base to 500-1000ml of tetrahydrofuran solution of 1 mole of p-nitrobenzyl acetate in 30-90 minutes at the temperature of minus 30-minus 40 DEG C to react for 1.5-2 hours and cooling the reactant to minus 70-minus 78 DEG C; dissolving 0.8-1 mole of (3S,4R)-3-[(1R)1-tert-butyldimethylsilyoxy ethyl]-4-[(1R)-1-1 methyl-methyl acetate]-oxetane-2-ketone into the 500-1000ml of tetrahydrofuran solution and cooling the solution to minus 70-minus 78 DEG C; and mixing the two kinds of solution to react for 2-3 hours, adding 10% by mass of 400-600ml of ammonium chloride to neutralize the reactant, washing the reactant with saturated sodium chloride solution, and after concentrating tetrahydrofuran under the vacuum condition of minus 0.095-minus 0.1MPa, adding n-hexane crystal to obtain the intermediate (3S,4R)-3-[(1R)-1-tert-butyldimethylsilyoxy ethyl]-4-[(1R)-1-methyl-3-(p-nitrobenzyloxy) carbonyl-2-oxopropyl]azetidine-2-ketone for carbapenem antibiotics. The method has the advantages of few reactions steps, low operation requirement, small usage amount of solvents and low cost.

Description

The preparation method of carbapenem antibiotic intermediate technical field The invention relates to a preparation method of a carbapenem antibiotic intermediate. Background technique Carbapenem antibiotics are the β-lactam antibiotics with the broadest antibacterial spectrum and the strongest antibacterial activity. The varieties that have been marketed in China include imipenem, meropenem, and panipenem, because of their anti-β- The stability and low toxicity of lactamase has become one of the most important antibacterial drugs for the treatment of severe bacterial infections, and it has received more and more attention and application in clinical practice. Where (3S,4R)-3-[(1R)-1-tert-butyldimethylsiloxyethyl)-4-[(1R)-1-methyl-3-(p-nitrobenzyloxy) Carbonyl-2-oxopropyl]azetidin-2-one (I) is a key intermediate in the synthesis of carbapenem antibiotics. (I) Patent CN101560219A discloses the synthesis method of (I), the step of which is to react mono-p-nitrobenzyl ...

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Problems solved by technology

The reaction uses mercury salt, which is toxic and pollutes the environment greatly

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