CN102212007A - Preparation method of high-purity 2-mehtylol methyl acrylate - Google Patents
Preparation method of high-purity 2-mehtylol methyl acrylate Download PDFInfo
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- CN102212007A CN102212007A CN2011100893652A CN201110089365A CN102212007A CN 102212007 A CN102212007 A CN 102212007A CN 2011100893652 A CN2011100893652 A CN 2011100893652A CN 201110089365 A CN201110089365 A CN 201110089365A CN 102212007 A CN102212007 A CN 102212007A
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- methyl acrylate
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Abstract
The invention discloses a preparation method of high-purity 2-mehtylol methyl acrylate. The method comprises the following steps: reacting trimethylphosphonoacetate with formaldehyde in a potassium carbonate aqueous solution; extracting with a first organic solvent; extracting with a second organic solvent; adding a slat for saturating a water phase; and adding a third organic solvent for extracting the product, concentrating for removing the solvent, and distilling at reduced pressure so as to obtain high-purity 2-mehtylol methyl acrylate. The yield of the product is 75%, the purity of the product is above 99.5%, and the content of any single impurity is less than 0.2%.
Description
Technical field
The present invention relates to a kind of preparation method of 2-methylol methyl acrylate.
Background technology:
2-hydroxymethyl propionic acid methyl esters is a kind of important medicine intermediate, can be used for synthetic anti-hepatitis b new drug Telbivudine, and the structure of 2-methylol methyl acrylate is as follows:
The preparation method of 2-methylol methyl acrylate is a lot.Wherein main preparation method has following two kinds:
Method one (Organic Letters 2006, Vol.83359-3362):
This method raw material is easy to get, but productive rate is very low, and side reaction is a lot.Be not suitable for suitability for industrialized production.
Method two (Organic synthesis):
This method technology is easy, yield height, suitability for industrialized production.But by the usually conduct method, product purity is low, and impurity is more.
Summary of the invention
The object of the present invention is to provide a kind of preparation method who makes the high high purity 2-methylol methyl acrylate of product purity.
Technical solution of the present invention is:
A kind of preparation method of high purity 2-methylol methyl acrylate is characterized in that: may further comprise the steps:
(1) phosphoryl 3-acetic acid methyl ester, formaldehyde are reacted in wet chemical;
(2) with first kind of organic solvent extraction;
(3) with second kind of solvent extraction;
(4) water adds salt loading;
(5) add the third organic solvent extraction product, concentrate to remove and desolvate, underpressure distillation obtains high purity 2-methylol methyl acrylate.
First kind of solvent is sherwood oil, normal hexane or hexanaphthene; The volume ratio of reaction solution and first kind of solvent is 1: 0.2-2.0.
Second kind of solvent is toluene, isopropyl ether or dimethylbenzene; The volume ratio of reaction solution and second kind of solvent is 1: 0.1-2.0.
The salt that adds is sodium-chlor, Repone K, calcium chloride or sodium sulfate; The weight ratio of reaction solution and salt is 1: 0.1-0.4.
The third solvent is methylene dichloride, chloroform or ethylene dichloride; The volume ratio of reaction solution and the third solvent is 1: 3-10.
Product yield of the present invention reaches 75%, and purity is more than 99.5%, and any single impurity is less than 0.2%.
The invention will be further described below in conjunction with embodiment.
Embodiment
Embodiment 1:
Add 30% formalin 400g and phosphoryl 3-acetic acid methyl ester 182g in 2 liters of there-necked flasks.Prepare 50% wet chemical 300g (150 gram salt of wormwood+150ml water), be chilled to room temperature after, be added dropwise in the there-necked flask, temperature is controlled at 5-10 ℃, drips 1-1.5 hour, drips off, and is warming up to room temperature naturally, stirs 1 hour.Reaction solution comes together in advance with the 100ml hexanaphthene, and water comes together in advance with 50ml toluene again.Water adds sodium-chlor 150g, uses chloroform extraction again three times, is respectively 300ml, 150ml, 150ml three times.Water discards, and chloroform merges mutually, and concentrating under reduced pressure desolventizes, and decompression steams product, obtains 99 gram products, yield 75%, purity 99.8%.
Embodiment 2:
Make the hexanaphthene in the example 1 into sherwood oil, other are constant, yield 78%, product purity 99.6%.
Embodiment 3:
Make the toluene in the example 1 into dimethylbenzene, other are constant, yield 79%, product purity 99.6%.
Embodiment 4:
Make the chloroform in the example 1 into methylene dichloride, other are constant, yield 80%, product purity 99.7%.
Embodiment 5:
A kind of preparation method of high purity 2-methylol methyl acrylate may further comprise the steps:
(1) phosphoryl 3-acetic acid methyl ester, formaldehyde are reacted in wet chemical;
(2) with first kind of organic solvent extraction;
(3) with second kind of solvent extraction;
(4) water adds salt loading;
(5) add the third organic solvent extraction product, concentrate to remove and desolvate, underpressure distillation obtains high purity 2-methylol methyl acrylate.
First kind of solvent is sherwood oil (or normal hexane or hexanaphthene); The volume ratio of reaction solution and first kind of solvent is 1: 0.2-2.0 (example 1: 0.2,1: 1,1: 2).
Second kind of solvent is toluene (or isopropyl ether or dimethylbenzene); The volume ratio of reaction solution and second kind of solvent is 1: 0.1-2.0 (example 1: 0.1,1: 1,1: 2).
The salt that adds is sodium-chlor (or Repone K or calcium chloride or sodium sulfate); The weight ratio of reaction solution and salt is 1: 0.1-0.4 (example 1: 0.1,1: 0.3,1: 0.4).
The third solvent is methylene dichloride (or chloroform or ethylene dichloride); The volume ratio of reaction solution and the third solvent is 1: 3-10 (example 1: 3,1: 6,1: 10).
Product yield is more than 75%, and purity is more than 99.5%, and any single impurity is less than 0.2%.
Product analysis method (vapor-phase chromatography):
Instrument: Agilent 6890N
Carrier gas: N
2
Splitting ratio: 30: 1
Post: HP-530m*0.32mm*0.25um
Vaporization temperature: 250 ℃
Detector temperature: 270 ℃
Heating schedule: 50 ℃ of initial temperatures, kept 2 minutes, 10 ℃/minute rise to 250 ℃ then, keep finishing in 5 minutes.
Claims (5)
1. the preparation method of a high purity 2-methylol methyl acrylate is characterized in that: may further comprise the steps:
Phosphoryl 3-acetic acid methyl ester, formaldehyde are reacted in wet chemical;
With first kind of organic solvent extraction;
With second kind of solvent extraction;
Water adds salt loading;
Add the third organic solvent extraction product, concentrate to remove and desolvate, underpressure distillation obtains high purity 2-methylol methyl acrylate.
2. the preparation method of high purity 2-methylol methyl acrylate according to claim 1 is characterized in that: first kind of solvent is sherwood oil, normal hexane or hexanaphthene; The volume ratio of reaction solution and first kind of solvent is 1:0.2-2.0.
3. the preparation method of high purity 2-methylol methyl acrylate according to claim 1 and 2 is characterized in that: second kind of solvent is toluene, isopropyl ether or dimethylbenzene; The volume ratio of reaction solution and second kind of solvent is 1:0.1-2.0.
4. the preparation method of high purity 2-methylol methyl acrylate according to claim 1 and 2 is characterized in that: the salt of adding is sodium-chlor, Repone K, calcium chloride or sodium sulfate; The weight ratio of reaction solution and salt is 1:0.1-0.4.
5. the preparation method of high purity 2-methylol methyl acrylate according to claim 1 and 2 is characterized in that: the third solvent is methylene dichloride, chloroform or ethylene dichloride; The volume ratio of reaction solution and the third solvent is 1:3-10.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2011100893652A CN102212007A (en) | 2011-04-11 | 2011-04-11 | Preparation method of high-purity 2-mehtylol methyl acrylate |
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| CN2011100893652A CN102212007A (en) | 2011-04-11 | 2011-04-11 | Preparation method of high-purity 2-mehtylol methyl acrylate |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106336357A (en) * | 2016-08-29 | 2017-01-18 | 启东东岳药业有限公司 | Preparation method of 2-hydroxymethyl methyl acrylate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0987282A2 (en) * | 1998-09-18 | 2000-03-22 | Nippon Shokubai Co., Ltd. | Acrylic monomer composition, acrylic copolymer, and heat resistant resin |
| EP1284263A1 (en) * | 2000-03-20 | 2003-02-19 | Consejo Superior De Investigaciones Cientificas | Derivatives of p- hydroxy phenyl propionic acid as antiproliferative agents |
| WO2011017561A1 (en) * | 2009-08-05 | 2011-02-10 | Biogen Idec Ma Inc. | Bicyclic aryl sphingosine 1-phosphate analogs |
-
2011
- 2011-04-11 CN CN2011100893652A patent/CN102212007A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0987282A2 (en) * | 1998-09-18 | 2000-03-22 | Nippon Shokubai Co., Ltd. | Acrylic monomer composition, acrylic copolymer, and heat resistant resin |
| EP1284263A1 (en) * | 2000-03-20 | 2003-02-19 | Consejo Superior De Investigaciones Cientificas | Derivatives of p- hydroxy phenyl propionic acid as antiproliferative agents |
| WO2011017561A1 (en) * | 2009-08-05 | 2011-02-10 | Biogen Idec Ma Inc. | Bicyclic aryl sphingosine 1-phosphate analogs |
Non-Patent Citations (3)
| Title |
|---|
| 《Tetrahedron》 20080209 Hannah E. Bartrum et al. Synthesis of beta2-homophenylalanine derivatives by Negishi cross-coupling reactions 第3701和3705页 1-5 第64卷, * |
| HANNAH E. BARTRUM ET AL.: "Synthesis of β2-homophenylalanine derivatives by Negishi cross-coupling reactions", 《TETRAHEDRON》 * |
| JOSE´ I. BORRELL ET AL.: "Synthesis and Biological Activity of 4-Amino-7-oxo-Substituted Analogues of 5-Deaza-5,6,7,8-tetrahydrofolic Acid and 5,10-Dideaza-5,6,7,8-tetrahydrofolic Acid", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106336357A (en) * | 2016-08-29 | 2017-01-18 | 启东东岳药业有限公司 | Preparation method of 2-hydroxymethyl methyl acrylate |
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Application publication date: 20111012 |