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Method for synthesizing clindamycin phosphate

A technology of clindamycin phosphate and a synthesis method, applied in the field of medicine and chemical industry, can solve the problems of long reaction period, waste, harsh reaction conditions, etc., achieves reduction of related impurities and production cost, and solves problems of poor solubility of powder and reaction The effect of cycle shortening

Inactive Publication Date: 2010-09-15
南阳普康药业有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method has the following disadvantages: First, the related substances of the finished product are unstable and high, the yield is low, the reaction conditions are harsh, and the reaction cycle is long, which makes it difficult to meet the needs of high-end products; Acetone, pyridine, resulting in higher cost
The 3rd, in the process of hydrolysis reaction, used a large amount of liquid caustic soda, caused unnecessary waste
The fourth is that the crystallization used is a one-time crystallization method, which causes problems such as poor crystal color and poor solubility of powder.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] ①. Ketal protection reaction: Take 30 kg of acetone, 10 kg of clindamycin hydrochloride alcoholate, and 17 kg of phosphorus oxychloride into the phosphorylation reactor, and cool to 0° C. and react for 5 hours.

[0018] ② Phosphorylation reaction: 6.5 kg of phosphorous oxychloride, 0.6 kg of 4-dimethylaminopyridine, 7 kg of pyridine, and 6 kg of triethylamine were added to the reactor in order, and the temperature was -2.0°C. 5.5 hours;

[0019] ③ Hydrolysis reaction: In the hydrolysis reactor, add 180kg purified water, lower the temperature to 3.0°C, start stirring, and then pump the above reaction liquid into the reactor. After pumping, the temperature is reacted at 40°C for 1.5 hours.

[0020] ④ Dilution: In the diluter, add 180kg of purified water to dilute the liquid, mix, and wait for adsorption;

[0021] ⑤ Adsorption and water washing: when resin is adsorbed, the adsorption flow rate is 40kg / L, after the adsorption is completed, wash with 70kg purified water, and the was...

Embodiment 2

[0028] ①Ketal protection reaction: Take 34kg of acetone, 10kg of clindamycin hydrochloride alcoholate, and 20kg of phosphorus oxychloride into the phosphorylation reactor, and cool down to -1.0℃, and react for 5.5 hours;

[0029] ② Phosphorylation reaction: Then respectively add phosphorus oxychloride 5.5kg, 4-dimethylaminopyridine 0.7kg, pyridine 8kg, and triethylamine 5.5kg in the order, and add them to the reactor at -1.0℃, Reaction for 5.5 hours;

[0030] ③ Hydrolysis reaction: In the hydrolysis reactor, add 180kg of purified water, lower the temperature to 1.0°C, turn on the stirring, then pump the above reaction liquid into the reactor, after pumping, react at 40°C for 2.0 hours;

[0031] ④ Dilution: In the diluter, add 200kg of purified water to dilute the liquid, mix, and wait for adsorption.

[0032] ⑤Adsorption and water washing: when resin is adsorbed, the adsorption flow rate is 40kg / L, after the adsorption is completed, wash with 65kg purified water, the washing flow rate...

Embodiment 3

[0039] ①Ketal protection reaction: Take 28kg of acetone, 10kg of clindamycin hydrochloride alcoholate, and 16kg of phosphorus oxychloride respectively into the phosphorylation reactor, and cool down to 0℃, and react for 5 hours;

[0040] ② Phosphorylation reaction: Then respectively add phosphorus oxychloride 5.5 kg, 4-dimethylaminopyridine 0.35 kg, pyridine 6.5 kg, and triethylamine 4.5 kg in order, and add them to the reactor at a temperature of 0°C, React for 5 hours;

[0041] ③ Hydrolysis reaction: In the hydrolysis reactor, add 200kg purified water, lower the temperature to 1.0°C, turn on the stirring, and then pump the above reaction liquid into the reactor, after pumping, the temperature is 38°C and react for 2 hours;

[0042] ④ Dilution: In the diluter, add 220kg of purified water to dilute the liquid, mix well, and wait for adsorption;

[0043] ⑤Adsorption and water washing: when resin is adsorbed, the adsorption flow rate is 35kg / L, after the adsorption is completed, wash wi...

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PUM

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Abstract

The invention discloses a method for synthesizing clindamycin phosphate, which comprises the following steps of: performing ketal protection reaction on clindamycin hydrochloride alcoholate at the temperature of between 2.0 below zero and 2.0 DEG C under the action of acetone and phosphorus oxychloride to form propylidene clindamycin; and performing esterification, hydrolysis, adsorption, washing, deabsorption, concentration, coarse crystallization, decoloration, refining and drying to obtain the finished product of clindamycin phosphate. Because a new catalyst 4-dimethylaminopyridine participates in the esterification in the rection system, the phosphorylating reaction is performed completely, and the conversion rate of raw materials is improved. Meanwhile, due to the secondary crystallization method, the problems of poor color grade and poor powder solubility are solved, and the operating conditions are mild and simple. By adopting triethylamine to replace partial pyridine, the esterification is pushed forwards; the reaction period is shortened; and importantly, related impurities in the finished product and the production cost are reduced, and the content is improved.

Description

Technical field [0001] The invention belongs to the technical field of medicine and chemical engineering, and particularly relates to a method for synthesizing clindamycin phosphate. Background technique [0002] Clindamycin phosphate is a derivative of clindamycin, which is widely used in the treatment of various infectious diseases caused by gram-positive bacteria and anaerobic bacteria. At present, in the synthetic process of producing Clindamycin Phosphate Phosphorus, the preparation method is as follows: Clindamycin Hydrochloride Alcoholate and Phosphorus oxychloride are subjected to a ketal protection reaction under the action of acetone solvent, and then esterified. After hydrolysis, adsorption, water washing, desorption, concentration, crystallization and drying, the finished product of clindamycin phosphate is obtained. This method has the following shortcomings: one is that the relevant substances in the finished product are unstable and high, the yield is low, the rea...

Claims

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Application Information

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IPC IPC(8): C07H15/16C07H1/02C07H1/06
Inventor 李静仁
Owner 南阳普康药业有限公司
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