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Method for preparing high-purity fosinopril sodium

A fosinopril sodium, high-purity technology is applied in the field of preparation of fosinopril sodium compounds, can solve the problems of low purity, unsuitable for industrial production, low yield of fosinopril sodium and the like, and achieves product yield and the effect of high purity and simple method

Inactive Publication Date: 2018-05-29
青岛市黄岛区中心医院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the purification methods of fosinopril sodium mainly include crystallization and column chromatography, and the yield of fosinopril sodium obtained by the above method is generally low, and the purity is not high, so it is not suitable for industrial production

Method used

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Examples

Experimental program
Comparison scheme
Effect test

no. 1 example

[0014] Put fosinopril sodium crude product 5g (purity is 95.5%) in reaction bottle, add 5% hydrochloric acid solution slowly, and stir, measure system pH value, when pH=4, add trimethyl phosphate 10g, fully Stir, then stand still for 30min, collect the organic phase, then continue to add 5g of trimethyl phosphate in the water phase, repeat the above operation 3 times, collect all the organic phase, add a 5% NaOH solution, stir well, and then slowly heat , control the temperature at 50°C and keep it for 5 minutes, a large amount of solids are produced, the system is cooled to room temperature, filtered to obtain a filter cake, washed with trimethyl phosphate, and dried in vacuum to obtain high-purity fosinopril sodium, collected The yield is 95.8%, and the purity is greater than 99.8%.

no. 2 example

[0016] Put 8 g of fosinopril sodium crude product (purity is 95.5%) in the reaction bottle, slowly add 10% sulfuric acid solution, and stir, measure the pH value of the system, when pH=3, add 12 g of triethyl phosphate, Stir fully, then stand still for 20min, collect the organic phase, then continue to add 8g triethyl phosphate in the water phase, repeat the above operation 3 times, collect all the organic phases, add a 10% sodium bicarbonate solution, stir well, and then Heat slowly, control the temperature at 80°C, and keep it for 10 minutes. A large amount of solids are produced. Cool the system to room temperature and filter to obtain a filter cake. Wash the filter cake with triethyl phosphate and dry it in vacuum to obtain high-purity fosinopril Sodium, the yield is 97.1%, and the purity is greater than 99.8%.

no. 3 example

[0018] Put 10g of fosinopril sodium crude product (purity is 95.5%) into the reaction bottle, slowly add 20% concentration of phosphoric acid solution, and stir, measure the pH value of the system, when pH=4, add diethyl ethyl phosphate 20g, fully stirred, then stand still for 10min, collect the organic phase, then continue to add 12g diethyl ethyl phosphate in the water phase, repeat the above operation 5 times, collect all the organic phases, add a concentration of 30% sodium hydrogen phosphate solution, Stir well, then heat slowly, control the temperature at 150°C, keep it for 30 minutes, a large amount of solids are produced, cool the system to room temperature, filter to obtain a filter cake, wash the filter cake with diethyl ethyl phosphate, and dry it in vacuum to obtain high Purity of fosinopril sodium, yield 97.9%, purity greater than 99.8%.

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PUM

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Abstract

The invention provides a method for preparing high-purity fosinopril sodium. Crude fosinopril sodium is first acidified, a phosphate solvent is then used as an extracting liquor for extraction, all organic phases are collected, an alkaline solution of sodium is then used for alkalization, and after filtration and washing, pure fosinopril sodium is obtained. Compared with the prior art, the methodhas the advantages of simplicity, high product yield and purity, suitability for industrial production and the like.

Description

technical field [0001] The invention relates to a preparation method of fosinopril sodium compound, which belongs to the field of medicinal chemistry. Background technique [0002] Fosinopril sodium, the English name is Fosinopril Sodium, the chemical name is 4-cyclohexyl-1-[(2-methyl-1-(propionyloxy)propoxy)(4-phenylbutyl)phosphine Sodium acetyl]-L-proline, the structural formula is: , has antihypertensive activity, is an angiotensin-converting enzyme inhibitor (ACEI), which can inhibit angiotensin-converting enzyme, reduce the concentration of angiotensin II and aldosterone, dilate peripheral blood vessels, reduce vascular resistance, and produce Buck effect. [0003] The purity of pharmaceutical compounds plays a vital role in whether they can be transformed into commercial drugs. Therefore, the purification process of pharmaceutical compounds is particularly important. At present, the purification methods of fosinopril sodium mainly include crystallization and column...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/572
Inventor 邹伟
Owner 青岛市黄岛区中心医院