CN1327974A - Process for rapidly racemizing naproxen methylester by microwave method - Google Patents
Process for rapidly racemizing naproxen methylester by microwave method Download PDFInfo
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- CN1327974A CN1327974A CN 01120902 CN01120902A CN1327974A CN 1327974 A CN1327974 A CN 1327974A CN 01120902 CN01120902 CN 01120902 CN 01120902 A CN01120902 A CN 01120902A CN 1327974 A CN1327974 A CN 1327974A
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- naproxen
- methyl ester
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Abstract
A process for quickly realizing full racemizing of methoxycarbonyl naproxen by microwave technique is disclosed, which features use of domistic microwave oven as heat source for high reaction speed and full racemizing and use of the two-phase system of non-polar organic solvent and less alcohol to create reaction system for easy separation of methoxy carbonyl naproxen from catalyst alkali.
Description
The present invention relates to a kind of chemical reaction method that utilizes the quick racemization Naproxen methyl ester of method of microwave heating.
(S)-(+)-and 2-(6-methoxyl group-2-naphthyl) propionic acid (Naproxen Base) is a kind of nonsteroidal anti-inflammatory drug of the 2-of belonging to arylpropionic acid compounds, it is the antiheumatic main medicine of antipyretic-antalgic, anti-inflammatory.The drug effect of its S configuration be 28 times of its R configuration (1.A.L.Margolin, Enzymes in the synthesisof chiral drugs.Enzyme.Microb.Technol.1993,15,266-279).
Naproxen Base can split by chemistry, the method for enzyme catalysis fractionation and asymmetric synthesis prepares.In recent years, utilize biotechnology to prepare optically active compound and become one of focus of research.The method that enzyme catalysis splits is at first the Naproxen Base esterification of racemization to be generated the naproxen ester of racemization, thereby utilize the naproxen ester of enzyme selectivity hydrolysis S type to produce methyl alcohol and the Naproxen Base (product) of S type and the naproxen ester (substrate) of remaining R type then.Product is separated the Naproxen Base that can obtain the product S type with substrate.The naproxen ester that the naproxen ester racemization of residue substrate R type is generated racemization is put in the reaction system again as reaction raw materials, thereby finishes a reaction cycle.
Generally speaking, the racemization of R type naproxen ester is by obtaining behind the reflux several hrs in the sodium hydroxide solution that it is dissolved in alcohol.Ezio, people such as B the have utilized this method racemization Naproxen Base ethoxy ethyl ester of R type, 11 hours consuming time (Ezio, B.Daniele, B.Pietro, C.et al, Biotechnologyand Bioengineer, 1991,38,659-664).
The present invention proposes a kind of method of utilizing microwave technology within very short time, to realize the complete racemization of Naproxen methyl ester.
Purpose of the present invention can be realized by following measure:
The non-polar organic solvent solution that in the alkaline alcoholic solution, adds S type or R type Naproxen methyl ester, add chlorosilane compounds additive then, this flask is put in the microwave oven, under 300-600W, can be obtained the Naproxen methyl ester of racemization in reflux 3-15 minute.
The highly basic alcoholic solution concentration that the present invention adopts is the 1-50 mol.
The concentration of S type Naproxen methyl ester in non-polar organic solvent that the present invention adopts be the 0.1-5 mmole/liter.
The microwave heating power that the present invention adopts is 300-600 watt.
The objective of the invention is to propose a kind of method of utilizing the quick racemization Naproxen methyl ester of microwave technology, solve problem of slow response in traditional racemization method.
Now further set forth the implementation of invention by most preferred embodiment.
Embodiment 1:
Under inert atmosphere, 100 milliliters of anhydrous methanols, 10 gram S type (or R type) Naproxen Bases and 9.6 gram trimethylchlorosilanes are added in 250 milliliters of round-bottomed flasks, stirred 24 hours under the room temperature.Steam the trimethylchlorosilane of anhydrous methanol and unreacted under the decompression, product with ethyl acetate extraction after, use 5% sodium bicarbonate aqueous solution and distilled water wash respectively, with the ethyl acetate anhydrous sodium sulfate drying.Dried ethyl acetate decompression is steamed, and remaining solid sherwood oil recrystallization gets 9.8 gram S type (or R type) Naproxen methyl esters.
20 milliliters of corresponding body excessive value is in the isooctane solution (8.8 mg/ml) of 10% R type Naproxen methyl ester, adds 0.5 gram sodium hydrate solid, 0.5 milliliter of anhydrous methanol and 20 microlitre trimethylchlorosilanes.The household microwave oven (2,450 million) that utilizes dribbling shape prolong is at 600 watts, reflux 4 minutes.Octane-iso is washed mutually, after the drying, is positioned over refrigerator and cooled and freezes crystalline substance, the Naproxen methyl ester that gets final product whitely.The corresponding body excessive value of measuring the product Naproxen methyl ester is 7.5%, and Naproxen methyl ester part racemization with this understanding is described owing to the reaction times is short.
Embodiment 2:
Naproxen methyl ester synthetic as described in the embodiment 1.
20 milliliters of corresponding body excessive value is in the isooctane solution (8.8 mg/ml) of 7.5% R type Naproxen methyl ester, adds 0.5 gram sodium hydrate solid, 0.5 milliliter of anhydrous methanol and 20 microlitre trimethylchlorosilanes.The household microwave oven (2,450 million) that utilizes dribbling shape prolong is at 375 watts, reflux 10 minutes.Octane-iso is washed mutually, after the drying, is positioned over refrigerator and cooled and freezes crystalline substance, the Naproxen methyl ester that gets final product whitely.The optically-active of measuring the product Naproxen methyl ester is zero, and Naproxen methyl ester racemization fully with this understanding is described.
Embodiment 3:
Naproxen methyl ester synthetic as described in the embodiment 1.
The Naproxen methyl ester that takes by weighing the corresponding body excessive value of 0.2 gram and be 100% S type is dissolved in 20 milliliters of octane-iso, adds 0.5 gram sodium hydrate solid, 0.5 milliliter of anhydrous methanol and 20 microlitre trimethylchlorosilanes.The household microwave oven (2,450 million) that utilizes dribbling shape prolong is at 375 watts, reflux 10 minutes.Octane-iso is washed mutually, after the drying, is positioned over refrigerator and cooled and freezes crystalline substance, the Naproxen methyl ester that gets final product whitely.Measuring the Naproxen methyl ester optically-active is zero, and the complete racemization of Naproxen methyl ester is described.
Claims (3)
1. the method for a process for rapidly racemizing naproxen methylester by microwave, it is characterized in that utilizing the microwave oven of certain power as thermal source, with highly basic is catalyzer, in non-polar organic solvent solution-a small amount of pure strong base solution two-phase system of Naproxen methyl ester, condition following within a short period of time of the complete racemization Naproxen methyl ester that has a small amount of additive to exist.
2. the method for claim 1 is characterized in that highly basic alcoholic solution concentration is the 1-50 mol.
3. the method for claim 1, it is characterized in that S type or the concentration of R type Naproxen methyl ester in non-polar organic solvent be the 0.1-5 mmole/liter.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01120902 CN1131196C (en) | 2001-06-08 | 2001-06-08 | Process for rapidly racemizing naproxen methylester by microwave method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01120902 CN1131196C (en) | 2001-06-08 | 2001-06-08 | Process for rapidly racemizing naproxen methylester by microwave method |
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| Publication Number | Publication Date |
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| CN1327974A true CN1327974A (en) | 2001-12-26 |
| CN1131196C CN1131196C (en) | 2003-12-17 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 01120902 Expired - Fee Related CN1131196C (en) | 2001-06-08 | 2001-06-08 | Process for rapidly racemizing naproxen methylester by microwave method |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101402561B (en) * | 2008-11-17 | 2011-07-20 | 浙江天新药业有限公司 | Racemization method for L-naproxen |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101880695B (en) * | 2010-02-26 | 2014-01-22 | 华东理工大学 | Method for preparing (S)-naproxen by enzyme resolution of racemic naproxen ester |
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2001
- 2001-06-08 CN CN 01120902 patent/CN1131196C/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101402561B (en) * | 2008-11-17 | 2011-07-20 | 浙江天新药业有限公司 | Racemization method for L-naproxen |
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| CN1131196C (en) | 2003-12-17 |
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