Method for synthesizing meropenem intermediate

A synthesis method and technology of meropenem side chain, applied in the direction of organic chemistry, etc., can solve the problems of poor stability, high energy consumption, long working hours, etc., and achieve the effects of improved stability and yield, low yield and long working hours

Inactive Publication Date: 2008-07-23
TIANJIN JINGYE FINE CHEM
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

In today's industrial production, meropenem is synthesized from the mother core MAP and the side chain H. Although there are many routes to synthesize the side chain H, most of them have long working hours, high energy consumption, poor stability and low yield. A series of problems, so the production and synthesis of meropenem side chain H with stable quality and high yield is an urgent problem to be solved at this stage

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  • Method for synthesizing meropenem intermediate

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Embodiment 1

[0024] Example 1: A method for synthesizing the side chain H of meropenem. The chemical name of the side chain H of meropenem is (2s, 4s)-1-(p-nitrobenzyloxycarbonyl)-2-dimethylformylamino-4 -Mercaptopyrrolidine, characterized in that 4R-hydroxyl-L-proline (1) is used as raw material to react with p-nitrobenzyl chloroformate under alkaline conditions to obtain amino-protected 4R-hydroxyl-L-proline Amino acid compound A (2), the intermediate (3) obtained by aminolysis after activating the carboxyl hydroxyl group of compound A (2) with isopropyl chloroformate, and then the intermediate (3) is acylated with methylsulfonyl chloride to obtain compound B (4), compound B (4) was substituted with potassium thioacetate to obtain compound C (5) with inverted 4-hydroxy configuration, and compound C (5) was subjected to alkaline hydrolysis to obtain meropenem side chain H (6).

[0025] A method for synthesizing meropenem side chain H, characterized in that the specific steps are as follow...

Embodiment 2

[0032] Example 2: A method for synthesizing the side chain H of meropenem. The chemical name of the side chain H of meropenem is (2s, 4s)-1-(p-nitrobenzyloxycarbonyl)-2-dimethylformylamino-4 -Mercaptopyrrolidine, characterized in that 4R-hydroxyl-L-proline (1) is used as raw material to react with p-nitrobenzyl chloroformate under alkaline conditions to obtain amino-protected 4R-hydroxyl-L-proline Amino acid compound A

[0033] (2), the intermediate (3) obtained by aminolysis after activation of the carboxyl hydroxyl group of compound A (2) by isopropyl chloroformate, and then the intermediate (3) is acylated with methylsulfonyl chloride to obtain compound B (4), Compound B (4) was substituted with potassium thioacetate to obtain compound C (5) with inverted 4-hydroxyl configuration, and compound C (5) was subjected to alkaline hydrolysis to obtain meropenem side chain H (6).

[0034] A method for synthesizing meropenem side chain H, characterized in that the specific steps a...

Embodiment 3

[0041] Example 3: A method for synthesizing the side chain H of meropenem. The chemical name of the side chain H of meropenem is (2s, 4s)-1-(p-nitrobenzyloxycarbonyl)-2-dimethylformylamino-4 -Mercaptopyrrolidine, characterized in that 4R-hydroxyl-L-proline (1) is used as raw material to react with p-nitrobenzyl chloroformate under alkaline conditions to obtain amino-protected 4R-hydroxyl-L-proline Amino acid compound A (2), the intermediate (3) obtained by aminolysis after activating the carboxyl hydroxyl group of compound A (2) with isopropyl chloroformate, and then the intermediate (3) is acylated with methylsulfonyl chloride to obtain compound B (4), compound B (4) was substituted with potassium thioacetate to obtain compound C (5) with inverted 4-hydroxy configuration, and compound C (5) was subjected to alkaline hydrolysis to obtain meropenem side chain H (6).

[0042] A method for synthesizing meropenem side chain H, characterized in that the specific steps are as follow...

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Abstract

The invention provides a synthesis method of a side chain H of a meropenem, which is characterized in that a new radical is introduced respectively for three functional groups of 4R hydroxy L hydroxyproline and a certain spatial configuration is kept. The synthesis method for the side chain H of a meropenem has the advantages of moderate process conditions, stable product quality, and high yield, which is applicable to the industrial production on a large scale.

Description

(1) Technical field: [0001] The present invention relates to a method for synthesizing a meropenem intermediate, in particular to a method for synthesizing side chain H of meropenem. (two) background technology: [0002] Meropenem (meropenem) is the first 1-β-methylcarbacyanase antibiotic used clinically. It has good chemical stability and is resistant to β-lactamase and renal dehydropeptide-I enzyme (DHP-I). Enzyme) is stable, has a broad antibacterial spectrum, and has obvious inhibitory effects on Gram-positive and negative bacteria. It is currently one of the first-selected drugs for the treatment of severe and multi-drug-resistant bacterial infections. In today's industrial production, meropenem is synthesized from the mother core MAP and the side chain H. Although there are many routes to synthesize the side chain H, most of them have long working hours, high energy consumption, poor stability and low yield. Therefore, the production and synthesis of meropenem side ch...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D207/14C07D477/20
Inventor 张铁柱穆慧敏勾兆光
Owner TIANJIN JINGYE FINE CHEM
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