CN106336357A - Preparation method of 2-hydroxymethyl methyl acrylate - Google Patents
Preparation method of 2-hydroxymethyl methyl acrylate Download PDFInfo
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- CN106336357A CN106336357A CN201610750553.8A CN201610750553A CN106336357A CN 106336357 A CN106336357 A CN 106336357A CN 201610750553 A CN201610750553 A CN 201610750553A CN 106336357 A CN106336357 A CN 106336357A
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- preparation
- methyl ester
- hydroxymethylacrylate
- ester according
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
Abstract
The invention discloses a preparation method of 2-hydroxymethyl methyl acrylate. The method includes the steps of firstly, mixing triphenyl phosphine, a catalyst and solvent, and dropwise adding 2-methyl bromoacetate to mixed liquid for temperature raising reaction; secondly, after reaction ends, being standing still and separating phases to separate out a methylbenzene phase; thirdly, dropwise adding a sodium hydroxide aqueous solution for cooling and crystallizing; fourthly, conducting suction filtration, and rinsing a filter cake with n-heptane to prepare methoxycarbonyl methylene triphenyl phosphoric chloride, namely a Wittig reagent; fifthly, adding the Wittig reagent to water, adding a formaldehyde aqueous solution, and dropwise adding a potassium carbonate aqueous solution for reaction; sixthly, filtering out triphenyl phosphine; seventhly, adding the solvent to filtrate for extraction; eighthly, concentrating an organic phase, and conducting reduced pressure distillation after removing the solvent to obtain 2-hydroxymethyl methyl acrylate. The raw materials are easy to obtain, production cost is low, and the method is suitable for industrial production and high in product yield.
Description
Technical field
The present invention relates to a kind of preparation method of 2- hydroxymethylacrylate methyl ester.
Background technology
2- hydroxymethylacrylate methyl ester is a kind of important medicine intermediate, can be used for new anti-hepatitis B medicament Telbivudine, 2-
The structure of hydroxymethylacrylate methyl ester is as follows:
The structure of 2- hydroxymethylacrylate methyl ester is as follows:
The preparation method of phenylalaninol is a lot.Wherein main preparation method has following two:
Method one (organic letters 2006, vol.83359-3362):.
The method raw material is easy to get, but reaction is very slow, and side reaction is a lot, is not suitable for industrialized production.
Method 2 (organic synthesis)
The method simple process, but " three wastes " amount is big, and product purity is low, and impurity is more.
Content of the invention
It is an object of the invention to provide a kind of raw material is easy to get, production cost is relatively low, is suitable for the 2- hydroxyl of industrialized production
The preparation method of methyl methacrylate.
The technical solution of the present invention is:
A kind of preparation method of 2- hydroxymethylacrylate methyl ester, is characterized in that: comprise the following steps:
(1) triphenyl phosphorus, catalysts and solvents mixing, 2- methyl bromoacetate are added drop-wise in mixed liquor, temperature reaction；
(2) after reaction terminates, stand split-phase, divide and go toluene phase；
(3) Deca sodium hydrate aqueous solution, crystallisation by cooling；
(4) sucking filtration, rinses filter cake with normal heptane, prepared methoxycarbonylmethylene triphenylphosphonium chloride, machine wittig reagent；
(5) wittig reagent is added to the water, adds formalin, Deca wet chemical reacts；
(6) it is filtered to remove triphenyl phosphorus；
(7) filtrate adds solvent extraction；
(8) organic faciess concentrate, and remove vacuum distillation after solvent, obtain 2- hydroxymethylacrylate methyl ester.
The molar ratio of 2- methyl bromoacetate and triphenyl phosphorus is 1:0.9～1:1.1.
2- methyl bromoacetate and molecular proportion of catalyst are 1:0.1～1:0.5.
2- methyl bromoacetate and molecular proportion of catalyst are 1:1.9～1:2.5.
Catalyst is sodium iodide or potassium iodide.
The concentration of formalin is 20-30%.
Reaction dissolvent is toluene, dimethylbenzene, dichloromethane or chloroform.
Raw material of the present invention is easy to get, and production cost is relatively low, is suitable for industrialized production；Product yield is high.
With reference to embodiment, the invention will be further described.
Specific embodiment
Embodiment 1:
First, the preparation of methoxycarbonylmethylene tri-phenyl-phosphorus bromide:
Add 88g (0.29mol) triphenylphosphine in there-necked flask, add 200ml toluene molten clear, then by 4.8g
(0.029mol) ki is dissolved in 200ml water and adds in toluene, Deca 44.4g (0.29mol) 2- methyl bromoacetate.Nitrogen is protected
Under be warming up to 65～75 DEG C, be incubated 20h.After insulation terminates, it is cooled to 50～60 DEG C, add 350ml water, split-phase.Aqueous phase is protected
Temperature, at 40 DEG C, is slowly added dropwise 268.4 gram of 10% sodium hydroxide solution, drips and is incubated 30min after finishing, sucking filtration, and filter cake is with 40ml positive heptan
Alkane rinses, and 50 DEG C of decompression dryings obtain 119.2 grams of yellow solid, yield 90%.
2nd, the preparation of 2- hydroxyethyl methacrylate:
119.2 grams of methoxycarbonylmethylene tri-phenyl-phosphorus bromides, 300ml water and 58 gram of 30% formalin is added in there-necked flask
Solution, slowly 266.8 grams of Deca 30% wet chemical at controlling 10-15 DEG C, drips and is incubated 6 hours at finishing 15-20 DEG C, filter
Remove insoluble matter (triphenyl phosphorus).Filtrate adds dichloromethane 500ml extraction, and organic faciess concentrate, and controls 70-90 after removing solvent
DEG C, vacuum distillation under vacuum 0.098mpa, obtain 25.7 grams of 2- hydroxymethylacrylate methyl ester (yield 85%).
Embodiment 2:
A kind of preparation method of 2- hydroxymethylacrylate methyl ester, comprises the following steps:
(1) triphenyl phosphorus, catalysts and solvents mixing, 2- methyl bromoacetate are added drop-wise in mixed liquor, temperature reaction；
(2) after reaction terminates, stand split-phase, divide and go toluene phase；
(3) Deca sodium hydrate aqueous solution, crystallisation by cooling；
(4) sucking filtration, rinses filter cake with normal heptane, prepared methoxycarbonylmethylene triphenylphosphonium chloride, machine wittig reagent；
(5) wittig reagent is added to the water, adds formalin, Deca wet chemical reacts；
(6) it is filtered to remove triphenyl phosphorus；
(7) filtrate adds solvent extraction；
(8) organic faciess concentrate, and remove vacuum distillation after solvent, obtain 2- hydroxymethylacrylate methyl ester.
The molar ratio of 2- methyl bromoacetate and triphenyl phosphorus is 1:0.9～1:1.1 (example 1:0.9,1:1,1:1.1).
2- methyl bromoacetate and molecular proportion of catalyst are 1:0.1～1:0.5 (example 1:0.1,1:0.3,1:0.5)；Or
2- methyl bromoacetate and molecular proportion of catalyst are 1:1.9～1:2.5 (example 1:1.9,1:2.3,1:2.5).
Catalyst is sodium iodide or potassium iodide.
The concentration of formalin is 20-30% (example 20%, 25%, 30%).
Reaction dissolvent is toluene, dimethylbenzene, dichloromethane or chloroform.
Claims (7)
1. a kind of preparation method of 2- hydroxymethylacrylate methyl ester, is characterized in that: comprise the following steps:
(1) triphenyl phosphorus, catalysts and solvents mixing, 2- methyl bromoacetate are added drop-wise in mixed liquor, temperature reaction；
(2) after reaction terminates, stand split-phase, divide and go toluene phase；
(3) Deca sodium hydrate aqueous solution, crystallisation by cooling；
(4) sucking filtration, rinses filter cake with normal heptane, prepared methoxycarbonylmethylene triphenylphosphonium chloride, machine wittig reagent；
(5) wittig reagent is added to the water, adds formalin, Deca wet chemical reacts；
(6) it is filtered to remove triphenyl phosphorus；
(7) filtrate adds solvent extraction；
(8) organic faciess concentrate, and remove vacuum distillation after solvent, obtain 2- hydroxymethylacrylate methyl ester.
2. the preparation method of 2- hydroxymethylacrylate methyl ester according to claim 1, is characterized in that: 2- methyl bromoacetate and
The molar ratio of triphenyl phosphorus is 1:0.9 ~ 1:1.1.
3. the preparation method of 2- hydroxymethylacrylate methyl ester according to claim 1, is characterized in that: 2- methyl bromoacetate and
Molecular proportion of catalyst is 1:0.1 ~ 1:0.5.
4. the preparation method of 2- hydroxymethylacrylate methyl ester according to claim 1, is characterized in that: 2- methyl bromoacetate and
Molecular proportion of catalyst is 1:1.9 ~ 1:2.5.
5. the preparation method of 2- hydroxymethylacrylate methyl ester according to claim 1, is characterized in that: catalyst is sodium iodide
Or potassium iodide.
6. the preparation method of 2- hydroxymethylacrylate methyl ester according to claim 1, is characterized in that: formalin dense
Spend for 20-30%.
7. the preparation method of 2- hydroxymethylacrylate methyl ester according to claim 1, is characterized in that: reaction dissolvent is first
Benzene, dimethylbenzene, dichloromethane or chloroform.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201610750553.8A CN106336357A (en) | 2016-08-29 | 2016-08-29 | Preparation method of 2-hydroxymethyl methyl acrylate |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610750553.8A CN106336357A (en) | 2016-08-29 | 2016-08-29 | Preparation method of 2-hydroxymethyl methyl acrylate |
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| CN106336357A true CN106336357A (en) | 2017-01-18 |
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| CN201610750553.8A Pending CN106336357A (en) | 2016-08-29 | 2016-08-29 | Preparation method of 2-hydroxymethyl methyl acrylate |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107759634A (en) * | 2017-10-31 | 2018-03-06 | 启东东岳药业有限公司 | A kind of Wittig tube- nurseries method |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6423806B1 (en) * | 1998-09-18 | 2002-07-23 | Nippon Shokubai Co., Ltd. | Acrylic monomer composition, acrylic copolymer, and heat resistant resin |
| WO2003064425A1 (en) * | 2002-01-28 | 2003-08-07 | Pfizer Japan Inc. | N-substituted spiropiperidine compounds as ligands for orl-1 receptor |
| JP2006342151A (en) * | 2005-05-12 | 2006-12-21 | Nippon Shokubai Co Ltd | Method for producing hydroxy-containing alkene |
| CN102212007A (en) * | 2011-04-11 | 2011-10-12 | 启东东岳药业有限公司 | Preparation method of high-purity 2-mehtylol methyl acrylate |
| CN102548409A (en) * | 2009-08-05 | 2012-07-04 | 比奥根艾迪克Ma公司 | Bicyclic aryl sphingosine 1-phosphate analogs |
-
2016
- 2016-08-29 CN CN201610750553.8A patent/CN106336357A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6423806B1 (en) * | 1998-09-18 | 2002-07-23 | Nippon Shokubai Co., Ltd. | Acrylic monomer composition, acrylic copolymer, and heat resistant resin |
| WO2003064425A1 (en) * | 2002-01-28 | 2003-08-07 | Pfizer Japan Inc. | N-substituted spiropiperidine compounds as ligands for orl-1 receptor |
| JP2006342151A (en) * | 2005-05-12 | 2006-12-21 | Nippon Shokubai Co Ltd | Method for producing hydroxy-containing alkene |
| CN102548409A (en) * | 2009-08-05 | 2012-07-04 | 比奥根艾迪克Ma公司 | Bicyclic aryl sphingosine 1-phosphate analogs |
| CN102212007A (en) * | 2011-04-11 | 2011-10-12 | 启东东岳药业有限公司 | Preparation method of high-purity 2-mehtylol methyl acrylate |
Non-Patent Citations (2)
| Title |
|---|
| 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
| 《TETRAHEDRON LETTERS》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107759634A (en) * | 2017-10-31 | 2018-03-06 | 启东东岳药业有限公司 | A kind of Wittig tube- nurseries method |
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Application publication date: 20170118 |
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