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Method for preparing naproxen

A technology of naproxen and carrier, applied in the field of preparation of naproxen, to achieve the effect of saving conversion rate, avoiding rapid inactivation, and realizing recycling

Inactive Publication Date: 2010-04-28
FANGXIA ENTERPRISE INFORMATION CONSULTING WUJIANG
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AI Technical Summary

Problems solved by technology

The lipase-catalyzed stereoselective hydrolysis of 2-arylpropionic acid drugs or the synthesis of corresponding esters is an efficient enantiomer resolution method, mainly including hydrolysis in water-organic solvent two-phase and micro-aqueous The transesterification method carried out in an organic solvent system, but it is still difficult to find an ideal organic solvent, which can not only ensure the high activity, stereoselectivity and stability of the enzyme, but also highly dissolve different polarity Substrates and products, so as to ensure that the reaction proceeds continuously and efficiently

Method used

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Examples

Experimental program
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Effect test

Embodiment Construction

[0007] 1. Immobilization of lipase: use adsorption method to immobilize lipase, dissolve 200mg lipase in 5ml phosphate buffer solution (pH7.5, 0.2mol / L), fully dialyze to remove small molecule additives such as lactose, then add amorphous porous Silica gel (bonded with phenethyl group) carrier, the carrier amount is 1~10g, stirred for 2h, after the lipase is completely absorbed, vacuum freeze-dried to remove water, and stored at 4°C for later use.

[0008] 2. The enzymatic hydrolysis of propraxen methyl ester in batch reactor: 200mg lipase immobilized with 2.5g carrier is added in the shaking flask of 100ml, contains 20ml naproxen methyl ester concentration in the shaking flask and is 10mg / ml of water-saturated 1-hexyl-3-methylimidazolium hexafluorophosphate was reacted at 30° C. and 150 r / min for 72 hours, and then the ionic liquid phase was poured out. Use isooctane (6 * 20ml) to extract the remaining substrate D-naproxen methyl ester in the ionic liquid, then use ether (6 ...

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Abstract

The invention provides a method for preparing naproxen, which uses a carrier, a catalyst and an organic solvent. The method is characterized in that: ionic liquid is used in place of the conventional catalyst and organic solvent; the hydrophobic carrier is used to cure lipase; isooctane and ethyl ether are used to extract a substrate remaining after reaction and the reaction product; the ethyl ether is removed by a vacuum method; an organic solvent is used for extraction; the recycling of the ionic liquid is realized; and at the same time, quick inactivation caused by the direct contact of the lipase with a polar organic solvent is avoided, the conversion rate is high and cost is saved.

Description

technical field [0001] The invention relates to a preparation method of medicine, in particular to a preparation method of naproxen. Background technique [0002] Naproxen is an anti-inflammatory drug, especially a basic chemical drug for antipyretic pain, anti-inflammation and anti-rheumatism. , it is very necessary to prepare optically pure drugs. The lipase-catalyzed stereoselective hydrolysis of 2-arylpropionic acid drugs or the synthesis of corresponding esters is an efficient enantiomer resolution method, mainly including hydrolysis in water-organic solvent two-phase and micro-aqueous The transesterification method carried out in an organic solvent system, but it is still difficult to find an ideal organic solvent, which can not only ensure the high activity, stereoselectivity and stability of the enzyme, but also highly dissolve different polarity Substrates and products, so as to ensure that the reaction is carried out continuously and efficiently. Contents of th...

Claims

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Application Information

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IPC IPC(8): C12P7/42
CPCY02P20/54
Inventor 谢瑜金珠韩璐
Owner FANGXIA ENTERPRISE INFORMATION CONSULTING WUJIANG
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