Preparation method of high purity valsartan

A valsartan, high-purity technology, applied in the field of preparation of high-purity valsartan, can solve the problems of undetected impurities, undetected, undetected chiral isomers, etc., to achieve environmental protection and simple operation , low cost effect

Active Publication Date: 2012-03-28
浙江新赛科药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although there are many documents about valsartan, there is no bibliographical report about the preparation method of valsartan with high

Method used

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  • Preparation method of high purity valsartan

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Experimental program
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Effect test

Embodiment 1

[0029] Embodiment 1 Preparation of valsartan crude product

[0030] Add 200g of valsartan methyl ester to a 3000ml three-necked flask, then add 790g of 10% potassium hydroxide aqueous solution, stir and react at 30°C for 8 hours, after the reaction is complete, cool down to below 15°C, dropwise add mass Concentrated hydrochloric acid with a percentage concentration of 36% was used to adjust the pH value to 1. After the adjustment, 1000 ml of ethyl acetate was added to extract and separate layers. The ethyl acetate layer was washed with an aqueous solution of sodium bicarbonate with a concentration of 5% by mass until weakly acidic. (pH value is 6.9), washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain crude valsartan.

Embodiment 2

[0031] Embodiment 2 Preparation of crude product of valsartan

[0032] Add 200g of valsartan methyl ester to a 3000ml three-necked flask, then add 790g of 10% potassium hydroxide aqueous solution, stir and react at 30°C for 8 hours, after the reaction is complete, cool down to below 15°C, dropwise add mass Concentrated hydrochloric acid with a percentage concentration of 32% was used to adjust the pH value to 1.5. After the adjustment, 1000ml of ethyl acetate was added to extract and separate layers, and the ethyl acetate layer was washed with an aqueous sodium bicarbonate solution with a concentration of 5% by mass until weakly acidic. (pH value is 6.5), washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain crude valsartan.

Embodiment 3

[0033] Example 3 The heavy refining of valsartan

[0034] Add 500ml of ethyl acetate to the crude valsartan obtained in Example 1, dissolve at 50°C, after dissolving, cool to 0°C to crystallize for 10 hours, centrifuge to obtain valsartan, yield 95%, valsartan Quality: related impurities 0.6%, chiral isomer 0.5%.

[0035] Add 100g of the above-prepared valsartan to a 1000ml three-neck flask, then add 600ml of ethyl acetate to dissolve at 50°C, after dissolving, cool down to 0°C to crystallize for 20 hours, centrifuge, and dry to obtain fine valsartan with a yield of 90% %, mass: related impurities were not detected, chiral isomers were not detected, and the residual ethyl acetate was 14000ppm.

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Abstract

The invention discloses a preparation method of high purity valsartan, which comprises the following steps: drying after a valsartan crude product is recrystallized through esters solvent, dissolving in inorganic base aqueous solution, then adjusting the inorganic base aqueous solution to be acidic by using hydrochloric acid, washing materials by using acid water solution after centrifugation, drying and crushing, and producing the high purity valsartan through centrifugation and drying. The method is simple to operate, the prepared valsartan is high in purity and has the quality that relevant impurities are not detected, chiral isomers are not detected, individual solution remains is smaller than 100 ppm, frequently-used reagents are used, the cost is low, the access is easy, the cost is lower, and meanwhile, the preparation method is beneficial to environmental protection and suitable for industrialized production.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a preparation method of high-purity valsartan. Background technique [0002] Valsartan (chemical name: N-(1-pentanoyl)-N-[4-[2-(1H-tetrazol-5-yl)phenyl]benzyl]-L-valine) available It is suitable for various types of hypertension, and has a good protective effect on the heart, brain and kidney. Hypertensive patients such as myocardial infarction, heart failure, proteinuria, and diabetes can be used routinely, and can be used in combination with diuretics (such as hydrochlorothiazide). The structural formula of valsartan is as follows: [0003] [0004] There are many relevant documents about valsartan, especially the documents about the synthesis route of valsartan. For example, Chinese patent ZL200710038346.0 discloses an improved method for synthesizing valsartan. N-[(2'-cyano-1,1'-biphenyl-4-yl)alkyl]-L-valine ester is used as a raw material, and is complete...

Claims

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Application Information

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IPC IPC(8): C07D257/04
Inventor 胡宇宏杨和军吕士华郭拥政许永平李海波肖俊
Owner 浙江新赛科药业有限公司
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