Method for refining fosfomycin phenylethylamine salt through cooling-solvating-out coupling crystallization

A left phosphorus right amine salt and crystallization technology, which is applied in the field of separation and purification of fine chemicals, can solve problems such as low equipment utilization, poor operating environment, and large solvent loss, and achieve low solvent loss, small solvent loss, and high volatility small effect

Active Publication Date: 2017-08-29
HUBEI XUNDA PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method overcomes the shortcomings of low equipment utilization rate, large solvent loss, poor operating environment and high energy consumption that are common

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] In order to verify the feasibility of the new process of the present invention and whether it can achieve a higher yield, a cooling-dissolution coupling crystallization experiment was carried out with left phosphorus and right ammonium salt refined salt under the premise of omitting the impurity removal step. First, 40.22 grams of left phosphorus and right ammonium salt refined salt (dry basis) were mixed with 121.2 grams of deionized water, and the mixed solution was stirred and heated to 75 ° C to completely dissolve, then allowed to cool naturally to room temperature, filtered and dried to obtain 26.7 grams of refined left phosphorus Right amine salt. Add 850g acetone in the filtrate gained in the previous step, filter after stirring for 30 minutes, obtain 5.44 gram of fine-quality left-phosphorus-right-ammonium salts after the filter cake is dried, add up to obtain 32.14 grams of fine-quality left-phosphorus-right-ammonium salts, total yield 79.9% (dry basis ). Ver...

Embodiment 2

[0024] Mix 40.22 grams of left phosphorus and right ammonium salt crude salt (wet basis) with 120.63 grams of deionized water, then add 8.11 grams of ethylene glycol, heat the mixed solution to 40-45 ° C, and then add 5.05 grams of Hydrogen peroxide, oxidation reaction 30min. After the oxidation reaction is completed, the temperature of the mixed solution is raised to 50°C, and then 0.6 g of activated carbon is added for decolorization, and the temperature of the mixed solution is raised to 70°C by continuing heating, and the activated carbon is sucked out after the materials are completely dissolved. Wash the activated carbon with an appropriate amount of deionized water, and combine the washing water and the filtrate. The mixed filtrate was naturally cooled to 25-26° C., filtered and dried to obtain 22.92 g of refined left phosphorus and right ammonium salt. Add 1000 gram of acetones to the filtrate of the previous step, filter after stirring for 30 minutes, obtain 8.69 gra...

Embodiment 3

[0026] Mix 5.00 grams of left phosphorus and right ammonium salt coarse salt (wet basis) with 15.26 grams of deionized water, then add 1.04 grams of ethylene glycol, heat the mixed solution to 40-45 ° C, then add 0.69 grams of hydrogen peroxide (50%), Oxidation for 30min. After the oxidation reaction is completed, the temperature of the mixed solution is raised to 50°C, and then 0.07 g of activated carbon is added for decolorization, and the temperature of the mixed solution is raised to 70°C by continuing heating, and the activated carbon is sucked out after the materials are completely dissolved. Wash the activated carbon with an appropriate amount of deionized water, combine the washing water and the filtrate, cool the mixed filtrate to 25-26° C., filter and dry to obtain 2.55 g of refined left phosphorus and right amine salt. Add 137 gram of acetones to the filtrate of the previous step, filter after stirring for 30 minutes, obtain 0.98 gram of fine-quality left-phosphorus...

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PUM

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Abstract

The invention relates to the technical field of compound separation and purification and in particular relates to a method for refining fosfomycin phenylethylamine salt through cooling-solvating-out coupling crystallization. The method comprises the following steps: with deionized water as a solvent, dissolving crude salt, then adding ethylene glycol, heating the solution to 40-45 DEG C, then oxidizing with hydrogen peroxide and decolorizing with activated carbon, stirring, heating the mixed solution to 70-75 DEG C, filtering the heated solution, cooling filtrate to 20-30 DEG C for crystallization, filtering, adding acetone into filtrate, carrying out solvating-out crystallization, filtering again, distilling filtrate, and then separating acetone and water to be recycled, wherein the yield of fosfomycin phenylethylamine salt refined product obtained after crystallization for twice reaches up to more than 80%. The method provided by the invention is simple in technology and can be carried out at normal temperature, cryogenic crystallization is not needed, energy consumption is low, the solvent, acetone, and water can be basically completely recycled, and fewer pollutants are discharged.

Description

technical field [0001] The invention relates to the technical field of separation and purification of fine chemicals, in particular to a method for refining left phosphorus and right ammonium salts through cooling-dissolution coupled crystallization. Background technique [0002] Levophosphorylamine salt is also known as fosfomycin L-dextral phenylethylamine salt, the scientific name is L-cis-1,2-epoxypropylphosphonic acid-D-α-phenylethylamine salt, which is the preparation of fosfomycin by Glamkowski method Sodium, fosfomycin calcium, fosfomycin trometamol and other new chromatographic sterilization drug intermediates. The industrial refinement of left phosphorus and right ammonium salt is realized by cooling crystallization with ethanol as solvent. Since the solubility of the left phosphorus and right ammonium salt in ethanol is small, and the whole system is easy to completely solidify at low temperature, the amount of ethanol is relatively large when actually dissolving...

Claims

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Application Information

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IPC IPC(8): C07F9/655C07C211/27C07C209/00
CPCC07F9/65505
Inventor 龙秉文谢竞祺王子乐丁一刚查树义杜治平刘生鹏邓伏礼
Owner HUBEI XUNDA PHARMA
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