CN105367435A - Preparation method for beta-alanine t-butyl ester hydrochloride - Google Patents
Preparation method for beta-alanine t-butyl ester hydrochloride Download PDFInfo
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- CN105367435A CN105367435A CN201510876840.9A CN201510876840A CN105367435A CN 105367435 A CN105367435 A CN 105367435A CN 201510876840 A CN201510876840 A CN 201510876840A CN 105367435 A CN105367435 A CN 105367435A
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- butyl ester
- alanine
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- ester hydrochloride
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
- C07C227/10—Formation of amino groups in compounds containing carboxyl groups with simultaneously increasing the number of carbon atoms in the carbon skeleton
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
The present invention discloses a preparation method for beta-alanine t-butyl ester hydrochloride. The method comprises the following steps of dissolving tert-butyl cyanoacetate in a solvent, adding an alkali into the solvent, then using Raney nickel to carry out catalytic hydrogenation, and after hydrogenation, removing the catalyst through filtration and obtaining a hydrogenated product after concentration; and dissolving the hydrogenated product into an organic solvent, dropwise adding an organic solvent of hydrogen chloride, and after the pH reaches 2-3, carrying out concentrating and drying under reduced pressure to obtain a target product. According to the method disclosed by the present invention, amino acid derivatives are prepared by using the catalytic hydrogenation, and the product is good in quality and high in yield; requirements on devices and reaction conditions are low, operations are simple, and the reaction conditions are mild, so that the method is suitable for industrial large-scaled production; and raw materials and reagents used are easily available and low in price, so that the product cost is low.
Description
Technical field
The present invention relates to medicine, organic chemistry filed, particularly relate to a kind of preparation method of Beta-alanine t-butyl ester hydrochloride.
Background technology
Beta-alanine t-butyl ester hydrochloride is a kind of important amino acid derivative, its medicine and pesticide intermediate preparation in have important application.Traditional preparation method has one, amino acid and the trimethyl carbinol react, and adopts DCC to participate in reaction as condensing agent or sulfur oxychloride; Two, amino acid and the tert-butyl ester carry out transesterification reaction; Three, amino acid and isobutene reaction.These methods are prepared this product and all be there is the problem that impurity is many, yield is low, cannot carry out suitability for industrialized production, and these also limit the further application of this product.The invention provides a kind of novel method preparing this material, solve this problem very well.
Summary of the invention
The object of the invention is to solve the problem that this compound is difficult to be prepared by traditional method, the present invention is by the following technical solutions: a kind of preparation method of Beta-alanine t-butyl ester hydrochloride, the cyanoacetic acid tert-butyl ester is comprised the steps: to dissolve in a solvent, and add alkali in a solvent, then shortening is carried out with Raney's nickel, after hydrogenation reaction, Filtration of catalyst, concentrates and obtains hydrogenation products; Be dissolved in by hydrogenation products in organic solvent, drip the organic solvent of hydrogenchloride, after pH reaches 2-3, concentrated, drying under reduced pressure obtains target product.
Reaction formula of the present invention is as follows:
Preferably, the solvent dissolving the cyanoacetic acid tert-butyl ester be methyl alcohol, ethanol, ethyl acetate, methyl-formiate any one.
Preferably, the consumption of solvent and the mass ratio of the cyanoacetic acid tert-butyl ester are 3-10:1, are preferably 4-9:1.
Preferably, the consumption of solvent and the mass ratio of the cyanoacetic acid tert-butyl ester are 5:1.
Preferably, the alkali added in solvent be potassium hydroxide, sodium hydroxide, salt of wormwood, ammonia, sodium-acetate any one.
Preferably, alkali addition is the 5-20% of cyanoacetic acid tert-butyl ester quality, is preferably 8-17%.
Preferably, the addition of Raney's nickel is the 5%-20% of cyanoacetic acid tert-butyl ester quality, is preferably 10%;
Preferably, the reaction pressure of hydrogenation reaction is 2-8Mpa, and temperature of reaction is 30-70 DEG C, and the reaction times is 2-10h.
Preferably, the reaction pressure of hydrogenation reaction is 4-6Mpa, and temperature of reaction is 40-60 DEG C, and the reaction times is 4-6h.
Preferably, described organic solvent be methyl alcohol-hydrogenchloride, ethanol-hydrogenchloride, ethyl acetate-hydrogenchloride, Virahol-hydrogenchloride any one.
Beneficial effect of the present invention:
1, the present invention adopts catalytic hydrogenation Preparation of amino acid derivative, good product quality, and yield is high;
2, the present invention is to equipment and reaction conditions, requires relatively low, simple to operate, and reaction conditions is gentle, is applicable to industrialization scale operation;
3, the starting material that the present invention is used and reagent, adopt raw material to be easy to get, low price, product cost is relatively low.
Embodiment
Below in conjunction with specific embodiment, the present invention is further elaborated.
Embodiment 1
In reactor, add the 200g cyanoacetic acid tert-butyl ester, add 600g methanol solution, potassium hydroxide 10g, add 10g Raney's nickel, sealed reactor, nitrogen replacement three times, hydrogen exchange three times.Being filled with hydrogen pressure is 2Mpa, is warming up to 30 DEG C, stirring reaction 2h, and midway is hydrogen make-up constantly.
After reaction terminates, Filtration of catalyst, filtrate concentrates, and adding 200g ethyl acetate, under cooling, add ethyl acetate-hydrogenchloride, is 3 to pH, concentrate system, separates out solid and dries.Obtain product 128g.
Embodiment 2
In reactor, add the 200g cyanoacetic acid tert-butyl ester, add 2kg ethanolic soln, sodium hydroxide 40g, add 40g Raney's nickel, sealed reactor, nitrogen replacement three times, hydrogen exchange three times.Being filled with hydrogen pressure is 8Mpa, is warming up to 70 DEG C, stirring reaction 10h, and midway is hydrogen make-up constantly.
After reaction terminates, Filtration of catalyst, filtrate concentrates, and adding 200g methyl alcohol, under cooling, add methyl alcohol-hydrogenchloride, is 3 to pH, concentrate system, separates out solid and dries.Obtain product 158g.
Embodiment 3
In reactor, add the 200g cyanoacetic acid tert-butyl ester, add 1.2kg ethanolic soln, add 20g Raney's nickel, sealed reactor, nitrogen replacement three times, hydrogen exchange three times.Being filled with hydrogen pressure is 5Mpa, is warming up to 50 DEG C, stirring reaction 6h, and midway is hydrogen make-up constantly.
After reaction terminates, Filtration of catalyst, filtrate concentrates, and adding 200g ethanol, under cooling, add ethanol-hydrogenchloride, is 3 to pH, concentrate system, separates out solid and dries.Obtain product 188g.
Embodiment 4
In reactor, add the 200g cyanoacetic acid tert-butyl ester, add 1kg methyl-formiate solution, add 20g Raney's nickel, sealed reactor, nitrogen replacement three times, hydrogen exchange three times.Being filled with hydrogen pressure is 4Mpa, is warming up to 50 DEG C, stirring reaction 6h, and midway is hydrogen make-up constantly.
After reaction terminates, Filtration of catalyst, filtrate concentrates, and adding 200g Virahol, under cooling, add Virahol-hydrogenchloride, is 3 to pH, concentrate system, separates out solid and dries.Obtain product 182g.
Embodiment 5
In reactor, add the 200g cyanoacetic acid tert-butyl ester, add 1kg2% methyl alcohol-ammonia solution, add 20g Raney's nickel, sealed reactor, nitrogen replacement three times, hydrogen exchange three times.Being filled with hydrogen pressure is 5Mpa, is warming up to 55 DEG C, stirring reaction 6h, and midway is hydrogen make-up constantly.
After reaction terminates, Filtration of catalyst, filtrate concentrates, and adding 200g ethyl acetate, under cooling, add ethyl acetate-hydrogenchloride, is 3 to pH, concentrate system, separates out solid and dries.Obtain product 198g.
Embodiment 6
In reactor, add the 200g cyanoacetic acid tert-butyl ester, add 2kg methanol solution, add 40g Raney's nickel, sealed reactor, nitrogen replacement three times, hydrogen exchange three times.Being filled with hydrogen pressure is 8Mpa, is warming up to 70 DEG C, stirring reaction 10h, and midway is hydrogen make-up constantly.
After reaction terminates, Filtration of catalyst, filtrate concentrates, and adding 200g Virahol, under cooling, add Virahol-hydrogenchloride, is 3 to pH, concentrate system, separates out solid and dries.Obtain product 162g.
Embodiment 7
In reactor, add the 200g cyanoacetic acid tert-butyl ester, add 1kg methyl-formiate solution, add 20g Raney's nickel, sealed reactor, nitrogen replacement three times, hydrogen exchange three times.Being filled with hydrogen pressure is 5Mpa, is warming up to 50 DEG C, stirring reaction 6h, and midway is hydrogen make-up constantly.
After reaction terminates, Filtration of catalyst, filtrate concentrates, and adding 200g Virahol, under cooling, add Virahol-hydrogenchloride, is 3 to pH, concentrate system, separates out solid and dries.Obtain product 175g.
Embodiment 8
In reactor, add the 200g cyanoacetic acid tert-butyl ester, add 1kg2% methyl alcohol-ammonia solution, add 25g Raney's nickel, sealed reactor, nitrogen replacement three times, hydrogen exchange three times.Being filled with hydrogen pressure is 4Mpa, is warming up to 55 DEG C, stirring reaction 5h, and midway is hydrogen make-up constantly.
After reaction terminates, Filtration of catalyst, filtrate concentrates, and adding 200g ethyl acetate, under cooling, add ethyl acetate-hydrogenchloride, is 3 to pH, concentrate system, separates out solid and dries.Obtain product 192g.
The foregoing is only preferred embodiment of the present invention; not thereby embodiments of the present invention and protection domain is limited; to those skilled in the art; the equivalent replacement that all utilizations description of the present invention is made and the scheme that apparent change obtains should be recognized, all should be included in protection scope of the present invention.
Claims (10)
1. a preparation method for Beta-alanine t-butyl ester hydrochloride, is characterized in that, comprises the steps: the cyanoacetic acid tert-butyl ester to dissolve in a solvent, and add alkali in a solvent, then carry out shortening, after hydrogenation reaction with Raney's nickel, Filtration of catalyst, concentrates and obtains hydrogenation products; Be dissolved in by hydrogenation products in organic solvent, drip the organic solvent of hydrogenchloride, after pH reaches 2-3, concentrated, drying under reduced pressure obtains target product.
2. the preparation method of a kind of Beta-alanine t-butyl ester hydrochloride as claimed in claim 1, is characterized in that, the solvent dissolving the cyanoacetic acid tert-butyl ester be methyl alcohol, ethanol, ethyl acetate, methyl-formiate any one.
3. the preparation method of a kind of Beta-alanine t-butyl ester hydrochloride as claimed in claim 1 or 2, is characterized in that, the consumption of solvent and the mass ratio of the cyanoacetic acid tert-butyl ester are 3-10:1, is preferably 4-9:1.
4. the preparation method of a kind of Beta-alanine t-butyl ester hydrochloride as claimed in claim 1 or 2, is characterized in that, the consumption of solvent and the mass ratio of the cyanoacetic acid tert-butyl ester are 5:1.
5. the preparation method of a kind of Beta-alanine t-butyl ester hydrochloride as claimed in claim 1, is characterized in that, the alkali added in solvent be potassium hydroxide, sodium hydroxide, salt of wormwood, ammonia, sodium-acetate any one.
6. the preparation method of a kind of Beta-alanine t-butyl ester hydrochloride as claimed in claim 1, is characterized in that, alkali addition is the 5-20% of cyanoacetic acid tert-butyl ester quality, is preferably 8-17%.
7. the preparation method of a kind of Beta-alanine t-butyl ester hydrochloride as claimed in claim 1, is characterized in that, the addition of Raney's nickel is the 5%-20% of cyanoacetic acid tert-butyl ester quality, is preferably 10%.
8. the preparation method of a kind of Beta-alanine t-butyl ester hydrochloride as claimed in claim 1, is characterized in that, the reaction pressure of hydrogenation reaction is 2-8Mpa, and temperature of reaction is 30-70 DEG C, and the reaction times is 2-10h.
9. the preparation method of a kind of Beta-alanine t-butyl ester hydrochloride as claimed in claim 1, is characterized in that, the reaction pressure of hydrogenation reaction is 4-6Mpa, and temperature of reaction is 40-60 DEG C, and the reaction times is 4-6h.
10. the preparation method of a kind of Beta-alanine t-butyl ester hydrochloride as claimed in claim 1, is characterized in that, described organic solvent be methyl alcohol-hydrogenchloride, ethanol-hydrogenchloride, ethyl acetate-hydrogenchloride, Virahol-hydrogenchloride any one.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510876840.9A CN105367435A (en) | 2015-12-03 | 2015-12-03 | Preparation method for beta-alanine t-butyl ester hydrochloride |
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| CN201510876840.9A CN105367435A (en) | 2015-12-03 | 2015-12-03 | Preparation method for beta-alanine t-butyl ester hydrochloride |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109970585A (en) * | 2019-04-29 | 2019-07-05 | 安徽安力肽生物科技有限公司 | A kind of preparation method of Beta-alanine ester type compound |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1566079A (en) * | 2003-06-18 | 2005-01-19 | 北京清华紫光英力化工技术有限责任公司 | Preparation method of N-(1-S-ethoxycarbonyl-3-phenyl propyl)-S-alanine |
| CN104470899A (en) * | 2012-03-09 | 2015-03-25 | 菲布罗根有限公司 | 4-hydroxy-isoquinoline compounds as HIF hydroxylase inhibitors |
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2015
- 2015-12-03 CN CN201510876840.9A patent/CN105367435A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1566079A (en) * | 2003-06-18 | 2005-01-19 | 北京清华紫光英力化工技术有限责任公司 | Preparation method of N-(1-S-ethoxycarbonyl-3-phenyl propyl)-S-alanine |
| CN104470899A (en) * | 2012-03-09 | 2015-03-25 | 菲布罗根有限公司 | 4-hydroxy-isoquinoline compounds as HIF hydroxylase inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| RENE´ W.M.ABEN,ET AL.: ""High-Pressure Promoted Cycloadditions of Enol Ethers and 3-Aryl-2-cyano-2-propenoates"", 《EUR.J.ORG.CHEM.》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109970585A (en) * | 2019-04-29 | 2019-07-05 | 安徽安力肽生物科技有限公司 | A kind of preparation method of Beta-alanine ester type compound |
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Application publication date: 20160302 |