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Preparation of clindamycinum phosphoester

A technology for clindamycin phosphate and lincomycin hydrochloride, which is applied in the field of preparation of clindamycin phosphate, can solve the problems of high environmental protection treatment pressure, high production cost, and high level of clindamycin contained in finished products, thereby reducing Finished product impurities and production costs, reducing environmental pressure, and reducing the effect of epicrine content

Active Publication Date: 2011-06-08
浙江天台药业股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method has the following disadvantages: (1) due to the large amount of phosphorus oxychloride used in the chlorination reaction stage, a large amount of trisodium phosphate is produced, so that the phosphorus content in the waste liquid is too high, the pressure of environmental protection treatment is large, and the finished product contains Epicline is too high, it is difficult to meet the needs of high-end customers; (2) Pyridine is used in large quantities in the esterification reaction, because the price of pyridine is high, so the production cost is relatively high

Method used

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  • Preparation of clindamycinum phosphoester
  • Preparation of clindamycinum phosphoester
  • Preparation of clindamycinum phosphoester

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] (1) Chlorination reaction: Take 160 billion lincomycin hydrochloride and 1000 L of chloroform, 227.2 kg of solid light, 1 kg of antioxidant AT-101 kg, and 240 L of DMF at 50-80 ° C for 15 hours. Then lower the temperature to 0°C.

[0031] (2) Alcoholization reaction: add drinking water 800L and mass concentration to the product of step (1) and be that 30% lye (sodium hydroxide aqueous solution) 400L is hydrolyzed at 55 ℃, layering, divide with the chloroform of 272L The organic layer was extracted twice, washed with water, concentrated at 75°C to obtain 1000L of chloroform, and then 160L of absolute ethanol was added for crystallization to obtain alcoholate. The alcoholate yield is 93%.

[0032] (3) Ketonization reaction: take 80Kg of the alcoholate obtained in step (2) and react with 320L of acetone and 29L of phosphorus oxychloride at -10°C for 6 hours;

[0033] (4) Esterification: react with 56L of phosphorus oxychloride, 80L of inhaled acetone, 60L of pyridine, an...

Embodiment 2

[0036] (1) Chlorination reaction: Take 80 billion lincomycin hydrochloride and 500 L of chloroform, 113.6 kg of solid light, 0.5 kg of antioxidant AT-10, and 120 L of DMF at 50-80 ° C for 25 hours. Then lower the temperature to 0°C.

[0037] (2) Alcoholization reaction: 400L of drinking water and 200L of 30% lye (sodium hydroxide aqueous solution) are hydrolyzed at 20°C in the solution obtained in step (1), and the layers are separated, and the organic layer is extracted twice with 136L of chloroform , washed with water, concentrated at 50°C to get 500L of chloroform, and then added 80L of absolute ethanol for crystallization to obtain alcoholate. Its alcoholate yield is 85%.

[0038] (3) Ketonization reaction: take 40Kg of the alcoholate obtained in step (2) and react with 160L of acetone and 14.5L of phosphorus oxychloride at 20°C for 7 hours;

[0039] (4) Esterification reaction: react with 28 L of phosphorus oxychloride, 40 L of acetone, 30 L of pyridine, and 35 L of tri...

Embodiment 3

[0042] (1) Chlorination reaction: Take 240 billion lincomycin hydrochloride and 1500 L of chloroform, 340.8 kg of solid light, 1.5 kg of antioxidant AT-10, and 360 L of DMF at 50-80 ° C for 40 hours. Then lower the temperature to 0°C.

[0043] (2) Alcoholation reaction: 1200L of drinking water and 600L of 30% sodium hydroxide solution are hydrolyzed at 40°C in the solution gained in step (1), and the layers are separated, and the organic layer is extracted twice with chloroform of 408L, washed with water, and Concentrate 1500L of chloroform at 65°C, then add 240L of absolute ethanol to crystallize to obtain alcoholate. Its alcoholate yield is 87%.

[0044] (3) Ketonization reaction: take 120Kg of the alcoholate obtained in step (2) and react with 480L of acetone and 43.5L of phosphorus oxychloride at 0°C for 8 hours;

[0045] (4) Esterification: react with 84 L of phosphorus oxychloride, 120 L of acetone, 90 L of pyridine, and 105 L of triethylamine at 0° C. for 12 hours.

...

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Abstract

The present invention provides a preparation method of clindamycin phosphate. The method provided by the present invention comprises the following processes: putting muriatic acid clindamycin and a solid light (C3Cl6O3) in a chloroform solvent to carry out chlorination reaction under the temperature of 50 to 80 DEG C; then alcoholizing and ketonizing; and finally under the co-catalysis of naphthyridine and triethylamine, esterifing the muriatic acid clindamycin and phosphorus oxychloride in an acetone solvent, hydrolyzing, absorbing and crystallizing, thus obtaining the clindamycin phosphate. The solid light is adopted to take part in the chlorination reaction in the reaction system of the invention, thus lightening the pressure of environment protection; simultaneously the content of epiclindamycin in the finished product is reduced; moreover, partial naphthyridine is replaced by the triethylamine, thus reducing the cost and improving the yield to a large extent.

Description

technical field [0001] The invention relates to clindamycin phosphate, in particular to a preparation method of clindamycin phosphate. Background technique [0002] Clindamycin phosphate can be used as a broad-spectrum antibiotic raw material. The preparation method of clindamycin phosphate commonly used at present is: first carry out chlorination reaction by lincomycin hydrochloride and phosphorus oxychloride in chloroform solvent, then through alcoholization, ketonization; Then under the catalysis of pyridine, It can be obtained after esterification with phosphorus oxychloride in acetone solvent, hydrolysis, adsorption and crystallization. This method has the following disadvantages: (1) due to the large amount of phosphorus oxychloride used in the chlorination reaction stage, a large amount of trisodium phosphate is produced, which leads to excessive phosphorus content in the waste liquid, and the pressure of environmental protection treatment is large, and the finished ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H15/16
Inventor 许凌月郭一平
Owner 浙江天台药业股份有限公司
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