Method for preparing imipenem

Abstract

The invention discloses a new method for preparing imipenem. The method comprises the following steps of: carrying out a Refortmasty reaction on an imipenem intermediate compound 4AA used as a starting material and an intermediate IX in the presence of a catalyst and obtaining an intermediate X through hydrolyzing; carrying out an N-H cabbeen insertion reaction on the intermediate X in the presence of a catalyst to obtain a double-ring parent nucleus III; in the presence of an organic base, phosphorylating to obtain an intermediate IV, directly reacting with cysteamine hydrochloride without separating, and then adding a proper solvent to obtain a solid solvent clathrate compound VI; directly carrying out condensation reaction on the solvent clathrate compound VI and imine benzyl oxide in the presence of base without removing the solvent to obtain an intermediate VII; and directly carrying out a catalytic hydrogenation reaction with the intermediate VII without separating to obtain a solution I containing the imipenem. The imipenem has a high content in the solution and can be crystallized by any known method in the field to obtain an imipenem-hydrate crystal.

Description

technical field The invention relates to an industrial preparation method of a compound, in particular to an industrial preparation method of the carbapenem antibiotic imipenem. Background technique Imipenem (I) is a carbapenem extended-spectrum β-lactam antibiotic developed by Merck Company, which has antibacterial effects on Gram-positive and Gram-negative aerobic and anaerobic bacteria. Its compound preparation with organic ion transport inhibitor cilastatin sodium (trade name: Taineng) is the first carbapenem β-lactam antibiotic on the market. Due to its excellent antibacterial properties, imipenem has attracted much attention, and there are many reports on its synthesis process. There are mainly the following schemes: Route 1: US4374772 discloses a method for obtaining imipenem directly through the reaction of thiamycin (II) and iminobenzyl ether. This method seems to be simple in steps, but it requires very strict reaction conditions, especially for pH control. I...

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Problems solved by technology

But at the same time, there is an extra step of solvent washing to remove the solvent in the clathrate, and the yield is affected

The patent does not mention the subsequent catalytic hydrogenation process

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