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Preparation method for precursor nitrogenous erythrocin of azithromycin

A technology for azithromycin and azithromycin, which is applied in the field of preparation of azithromycin precursor azithromycin, can solve the problems of affecting the quality of the target product, reducing the yield, and incomplete separation of the boride and the target product, and improving the yield. , mild process conditions, high efficiency

Inactive Publication Date: 2013-07-24
HEZE CITY FANGMING PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Another feature of acidic hydrolysis is that borides and target products are not completely separated, and more of them exist in the product in the form of impurities, which seriously affects the quality of the target product and reduces the yield.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0011] Add 800kg of purified water into the reaction kettle, add 16kg of hydrolysis-promoting agent sorbitol, dissolve it, add 1000L of chloroform phase containing 160kg of azoerythromycin borate into the reaction kettle, cool down to -10°C, and add 10% hydrochloric acid to PH = 1.5, after 5 minutes, quantitatively add 20% sodium hydroxide solution to PH = 9.7-10.0 at one time, stir for 5 minutes, stand still and separate the phases, and then extract the separated water phase with 100L chloroform, combine the chloroform phases, separate The water phase was removed, and the chloroform phase was taken for analysis. After HPLC detection, the acid decomposition product was 2.1%, the boride was 0.9%, and the yield was 96.1%.

Embodiment 2

[0013] Put 800kg of purified water into the reaction kettle, add 16kg of hydrolysis agent mannitol, dissolve it, add 1000L of dichloromethane phase containing 160kg of azoerythromycin borate into the reaction kettle, cool down to 0°C, and add 10% hydrochloric acid After 8 minutes to pH = 1.5, add 20% sodium hydroxide solution quantitatively at one time to pH = 9.7-10.0, stir for 5 minutes, let stand to separate phases, and extract the separated water phase with 100L dichloromethane, dichloromethane The methane phases were combined, and the dichloromethane phase was analyzed by HPLC. The acid decomposition product was 0.98%, the boride was 0.5%, and the yield was 97.0%.

Embodiment 3

[0015] Put 800kg of purified water into the reaction kettle, add 8kg of hydrolysis agent sorbitol, dissolve it, add 1000L of 1,2-dichloroethane containing 160kg of azoerythromycin borate into the reaction kettle, cool down to 0°C, add 10% hydrochloric acid to PH = 1.5, after 15 minutes, quickly add 20% sodium hydroxide solution to PH = 9.7-10.0, stir for 5 minutes, stand still to separate phases, and then extract the water phase with 100L 1,2-dichloroethane, The 1,2-dichloroethane phases were combined, and the 1,2-dichloroethane phase was analyzed. After HPLC detection, the acid decomposition product was 8%, the boride was 2%, and the yield was 90%.

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PUM

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Abstract

The invention belongs to the technical field of pharmacy, and discloses a preparation method for the precursor nitrogenous erythrocin of azithromycin. The preparation method is characterized in that in the presence of a hydrolysis accelerant and in a two-phase solvent, the hydrolysis speed is increased, and the pH is instantly adjusted, so as to realize thorough separation for the product and borides, and the product is improved in both quality and yield. The method is simple in process, the content of acidic degradation products is less than 2.0%, the content of the borides is less than 1.0%, the yield is 97%, and the product can be directly used for synthesising azithromycin via methylation, and is suitable for industrialized production.

Description

technical field [0001] The invention belongs to the technical field of pharmacy and relates to a preparation method of azithromycin precursor azoerythromycin. Background technique [0002] Azithromycin (N-methyl-11-aza-10-deoxy-10-dihydroerythromycin A) is a macrolide antibiotic widely used in respiratory system, urinary system, skin and soft tissue infections, etc., USA The FDA approved the first-line drug to replace penicillin as an anti-infective drug, and it can also treat mycobacterial infection in AIDS patients. [0003] Its chemical synthesis mainly includes the following steps: using erythromycin thiocyanate A as a starting material, generating azithromycin through oximation, Beckmann rearrangement, potassium borohydride reduction, acid hydrolysis and methylation. [0004] Literature (Ma Min, Yao Guowei, Deng Yulin. Research on borate hydrolysis in the synthesis of azithromycin [J]. Fine Chemical Industry, 2006, 23 (6): 558-587.) reported that in the process of acid...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H17/00C07H1/00
Inventor 朱文祥刘云霞
Owner HEZE CITY FANGMING PHARMA