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Process for preparing doripenem

A preparation process, technology of doripenem, applied in the field of preparation process of doripenem, can solve problems such as low product yield, fast reaction speed, difficult post-processing, etc. Worker Health Effects

Inactive Publication Date: 2014-03-12
ANHUI YOUCARE KAIYUE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These methods have fast reaction speed, many degradation products, low product yield, poor purity, and difficult post-processing.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] (1) Add 6L of tetrahydrofuran into a 50L high-pressure hydrogenation reactor, then add 2.55kg of doripenem condensate, then add 6L of tetrahydrofuran, stir to dissolve it completely, then add 408g of magnesium chloride hexahydrate, 2.55 kg of 10% Pd / C (water content 55.4%) and 11.6L of distilled water and 7L of tetrahydrofuran, close the reaction kettle, pass the refrigerant, pass the hydrogen, exhaust the air once, start stirring, pass the hydrogen, and control the pressure to 15kg / cm 2 During the reaction process, the temperature of the system was controlled below 25°C. After 2 hours, the hydrogen absorption was complete, and the cooling liquid was continued to reduce the temperature of the reaction system to -5°C. The catalyst was removed by rapid filtration under reduced pressure, and the catalyst was washed with 3.8L of distilled water. Extract the mother liquor with ethyl acetate four times (19L, 12L, 6L, 6L), then extract the mother liquor with n-butanol three t...

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PUM

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Abstract

The invention relates to the technical field of pharmacy, in particular to a process for preparing doripenem. The process comprises the following steps: taking tetrahydrofuran, a doripenem condensation compound, magnesium chloride hexahydrate, 10% Pd / C and distilled water as raw materials, carrying out a series of reactions; extracting an aqueous phase by using ethyl acetate and n-butyl alcohol; washing with propyl alcohol to obtain a crude product of doripenem, treating with activated carbon and propyl alcohol, thus obtaining sterile doripenem. The operation is simple, is favorable for the environment protection and health of workers, and the raw materials are readily available and low in price; therefore, the process is more suitable for industrial production of doripenem.

Description

technical field [0001] The invention relates to the technical field of pharmacy, in particular to a preparation process of doripenem. Background technique [0002] Doripenem, a carbapenem antibiotic in the β-lactam class, is used to treat various inflammations. US5317046 first disclosed the doripenem compound and its preparation method, using the aluminum chloride deprotection method, which requires a low temperature of -60 to -30°C, and the post-reaction treatment process requires styrene-divinylbenzene copolymer resin Column chromatography purification. The raw materials used in this method are not easy to obtain, and the reaction requires special refrigeration equipment, reaction equipment and column chromatography equipment, which has high requirements for industrial production and high cost. In the CN101935321 reaction system, an organic base-3,5-lutidine is used, and a solvent crystallization method is adopted to obtain a final product. These methods have fast react...

Claims

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Application Information

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IPC IPC(8): C07D477/20C07D477/02
CPCC07D477/02C07D477/20
Inventor 周如国
Owner ANHUI YOUCARE KAIYUE PHARMA
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