CN109970585A - A kind of preparation method of Beta-alanine ester type compound - Google Patents
A kind of preparation method of Beta-alanine ester type compound Download PDFInfo
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- CN109970585A CN109970585A CN201910353559.5A CN201910353559A CN109970585A CN 109970585 A CN109970585 A CN 109970585A CN 201910353559 A CN201910353559 A CN 201910353559A CN 109970585 A CN109970585 A CN 109970585A
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- cyanoacetate
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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
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
The invention belongs to chemical technology fields, more particularly to a kind of preparation method of Beta-alanine ester type compound, include the following steps: a) to dissolve cyanoacetate in solvent I, alkaline matter is added and Raney's nickel carries out catalytic hydrogenation reaction, it filters after reaction and filtrate is concentrated, obtain product A；B) product A is dissolved in solvent II, II solution of solvent of hydrogen chloride is added dropwise, after system pH is 2~3, stopped being added dropwise, obtain mixed liquid B；C) mixed liquid B is concentrated, is dried under reduced pressure, obtain target product.Using the above scheme, amino acid derivativges are prepared using cyanoacetate catalytic hydrogenation, easy to operate, mild condition, low for equipment requirements, input cost is low；Raw material is easy to get, and price is lower, reduces operation cost；Reaction-ure conversion-age is high, product yield high, is suitble to industrialization large-scale production.
Description
Technical field
The invention belongs to chemical technology fields, and in particular to a kind of preparation method of Beta-alanine ester type compound.
Background technique
Beta-alanine ester type compound is a kind of important amino acid derivativges, in the preparation of medicine and pesticide intermediate
Aspect has important application.Traditional preparation method has: one, amino acid is reacted with alcohol, using DCC as condensing agent or chlorine
Change sulfoxide and participates in reaction；It two, is that amino acid and hydrogen chloride -ol liquid carry out esterification preparation；Three, amino acid and alcohol in sulfuric acid or
Esterification is carried out under the catalysis of the Bronsted acids such as p-methyl benzenesulfonic acid.The impurity in products of these preparation methods is more, yield is low, therefore,
The problem of raising reaction-ure conversion-age and product yield are technical staff's urgent need to resolve.
Summary of the invention
It is an object of that present invention to provide a kind of simple process, reaction-ure conversion-age is high, Beta-alanine ester of product yield high
The preparation method of class compound.
To achieve the above object, a kind of the technical solution adopted by the present invention are as follows: preparation side of Beta-alanine ester type compound
Method includes the following steps:
A) cyanoacetate is dissolved in solvent I, alkaline matter is added and Raney's nickel carries out catalytic hydrogenation reaction, after reaction
It filters and filtrate is concentrated, obtain product A；
B) product A is dissolved in solvent II, II solution of solvent of hydrogen chloride is added dropwise, after system pH is 2~3, stop drop
Add, obtains mixed liquid B；
C) mixed liquid B is concentrated, is dried under reduced pressure, obtain target product.
Using the above scheme, amino acid derivativges are prepared using cyanoacetate catalytic hydrogenation, easy to operate, mild condition,
Low for equipment requirements, input cost is low；Raw material is easy to get, and price is lower, reduces operation cost；Reaction-ure conversion-age is high, produces
Object high income is suitble to industrialization large-scale production.
Specifically, in the step a), the pressure of hydrogenation reaction is 2~8Mpa, and temperature is 30~70 DEG C, the reaction time
For 2~10h.Cyanoacetate is one of methyl cyanoacetate, ethyl cyanoacetate, the cyanoacetic acid tert-butyl ester；Solvent I is methanol, second
One of alcohol, ethyl acetate, methyl formate；The mass ratio of cyanoacetate and solvent I is 1:(3~10)；Alkaline matter is hydrogen
One of potassium oxide, sodium hydroxide, potassium carbonate, ammonia, sodium acetate, sodium formate, sodium methoxide, sodium ethoxide；Alkaline matter adds
Dosage is the 5%~20% of cyanoacetate quality；The additive amount of Raney's nickel is the 5%~20% of cyanoacetate quality.It needs to infuse
Meaning, which carried out under the atmosphere of anaerobic, specifically uses nitrogen and/or hydrogen by the air displacement in reaction vessel
Out, in the pressure for being filled with nitrogen or hydrogen control reaction system.
In the step b), solvent II is one of methanol, ethyl alcohol, ethyl acetate, isopropanol.
Specific embodiment
Embodiment 1
200g methyl cyanoacetate, 600g methanol, 10g potassium hydroxide, 10g Raney's nickel are added into reaction vessel, will react
Container sealing, three times with nitrogen displacement, then three times with hydrogen displacement, being then charged with hydrogen to pressure is 2Mpa, is warming up to 30 DEG C,
It is stirred to react 2h, continues hydrogen make-up in reaction process and maintains pressure 2Mpa, until reaction pressure no longer changes, reaction terminates,
Catalyst is filtered away, colloid is concentrated filtrate to, 200g ethyl acetate is added, the second of hydrogen chloride is added dropwise under cooling condition
System is concentrated into half, solid is precipitated, dries to obtain Beta-alanine methyl esters salt by acetate solution until pH stops being added dropwise after being 3
Hydrochlorate 128g, measuring purity is 99.0%, continues to be concentrated, obtains Beta-alanine methyl ester hydrochloride 90g, and measuring purity is 98.6%,
Calculating methyl cyanoacetate conversion ratio is 77.4%.
Embodiment 2
200g ethyl cyanoacetate, 2000g ethyl alcohol, 40g sodium hydroxide, 40g Raney's nickel are added into reaction vessel, will react
Container sealing, three times with nitrogen displacement, then three times with hydrogen displacement, being then charged with hydrogen to pressure is 8Mpa, is warming up to 70 DEG C,
It is stirred to react 10h, continues hydrogen make-up in reaction process and maintains pressure 8Mpa, until reaction pressure no longer changes, reaction terminates,
Catalyst is filtered away, colloid is concentrated filtrate to, 200g methanol is added, the methanol that hydrogen chloride is added dropwise under cooling condition is molten
System is concentrated into half, solid is precipitated, dries to obtain Beta-alanine carbethoxy hydrochloride by liquid until pH stops being added dropwise after being 3
158g, measuring purity is 98.6%, continues to be concentrated, obtains Beta-alanine methyl ester hydrochloride 100g, and measuring purity is 98.6%, is calculated
Methyl cyanoacetate conversion ratio is 95.0% out.
Embodiment 3
The 200g cyanoacetic acid tert-butyl ester, 1200g ethyl alcohol, 100g sodium acetate, 20g Raney's nickel are added into reaction vessel, it will be anti-
Container is answered to seal, three times with nitrogen displacement, then three times with hydrogen displacement, being then charged with hydrogen to pressure is 5Mpa, is warming up to 50
DEG C, it is stirred to react 6h, continues hydrogen make-up in reaction process and maintains pressure 5Mpa, until reaction pressure no longer changes, reaction knot
Beam filters away catalyst, concentrates filtrate to colloid, and 200g ethyl alcohol is added, the second of hydrogen chloride is added dropwise under cooling condition
System is concentrated into half, solid is precipitated, dries to obtain Beta-alanine tert-butyl ester hydrochloric acid by alcoholic solution until pH stops being added dropwise after being 3
Salt 188g, measuring purity is 99.0%, continues to be concentrated, obtains Beta-alanine t-butyl ester hydrochloride 55g, and measuring purity is 98.8%,
Calculating cyanoacetic acid tert-butyl ester conversion ratio is 94.4%.
Embodiment 4
200g methyl cyanoacetate, 1000g methanol, 100g sodium methoxide, 20g Raney's nickel are added into reaction vessel, will react
Container sealing, three times with nitrogen displacement, then three times with hydrogen displacement, being then charged with hydrogen to pressure is 4Mpa, is warming up to 50 DEG C,
It is stirred to react 6h, continues hydrogen make-up in reaction process and maintains pressure 4Mpa, until reaction pressure no longer changes, reaction terminates,
Catalyst is filtered away, colloid is concentrated filtrate to, 200g isopropanol is added, the isopropyl of hydrogen chloride is added dropwise under cooling condition
System is concentrated into half, solid is precipitated, dries to obtain Beta-alanine methyl ester hydrochloride by alcoholic solution until pH stops being added dropwise after being 3
182g, measuring purity is 99.0%, continues to be concentrated, obtains Beta-alanine methyl ester hydrochloride 92g, and measuring purity is 98.6%, is calculated
Methyl cyanoacetate conversion ratio is 97.3% out.
Embodiment 5
Methanol-ammonia solution, the 20g Raney's nickel of 200g methyl cyanoacetate, 1000g 2% are added into reaction vessel, it will
Reaction vessel sealing, three times with nitrogen displacement, then three times with hydrogen displacement, being then charged with hydrogen to pressure is 5Mpa, is warming up to
55 DEG C, it is stirred to react 6h, continues hydrogen make-up in reaction process and maintains pressure 5Mpa, until reaction pressure no longer changes, is reacted
Terminate, filter away catalyst, concentrate filtrate to colloid, 200g ethyl acetate is added, chlorination is added dropwise under cooling condition
System is concentrated into half, solid is precipitated, dries to obtain Beta-alanine by the ethyl acetate solution of hydrogen until pH stops being added dropwise after being 3
Methyl ester hydrochloride 198g, measuring purity is 99.0%, continues to be concentrated, obtains Beta-alanine methyl ester hydrochloride 72g, measuring purity is
98.7%, calculating methyl cyanoacetate conversion ratio is 95.8%.
Embodiment 6
200g methyl cyanoacetate, 2000g methanol, 100g sodium methoxide, 40g Raney's nickel are added into reaction vessel, will react
Container sealing, three times with nitrogen displacement, then three times with hydrogen displacement, being then charged with hydrogen to pressure is 8Mpa, is warming up to 70 DEG C,
It is stirred to react 10h, continues hydrogen make-up in reaction process and maintains pressure 8Mpa, until reaction pressure no longer changes, reaction terminates,
Catalyst is filtered away, colloid is concentrated filtrate to, 200g isopropanol is added, the isopropyl of hydrogen chloride is added dropwise under cooling condition
System is concentrated into half, solid is precipitated, dries to obtain Beta-alanine methyl ester hydrochloride by alcoholic solution until pH stops being added dropwise after being 3
162g, measuring purity is 99.2%, continues to be concentrated, obtains Beta-alanine methyl ester hydrochloride 92g, and measuring purity is 98.7%, is calculated
Methyl cyanoacetate conversion ratio is 90.2% out.
Embodiment 7
200g methyl cyanoacetate, 1000g methyl formate, 100g sodium formate, 20g Raney's nickel are added into reaction vessel, it will
Reaction vessel sealing, three times with nitrogen displacement, then three times with hydrogen displacement, being then charged with hydrogen to pressure is 5Mpa, is warming up to
50 DEG C, it is stirred to react 6h, continues hydrogen make-up in reaction process and maintains pressure 5Mpa, until reaction pressure no longer changes, is reacted
Terminate, filter away catalyst, concentrate filtrate to colloid, 200g isopropanol is added, hydrogen chloride is added dropwise under cooling condition
Aqueous isopropanol system is concentrated into half, solid is precipitated, dries to obtain Beta-alanine methyl esters until pH stops being added dropwise after being 3
Hydrochloride 175g, measuring purity is 99.0%, continues to be concentrated, obtains Beta-alanine methyl ester hydrochloride 73g, measuring purity is
98.6%, calculating methyl cyanoacetate conversion ratio is 96.4%.
Embodiment 8
Methanol-ammonia solution, 25 Raney's nickels of 200g methyl cyanoacetate, 1000g 2% are added into reaction vessel, it will
Reaction vessel sealing, three times with nitrogen displacement, then three times with hydrogen displacement, being then charged with hydrogen to pressure is 4Mpa, is warming up to
55 DEG C, it is stirred to react 5h, continues hydrogen make-up in reaction process and maintains pressure 4Mpa, until reaction pressure no longer changes, is reacted
Terminate, filter away catalyst, concentrate filtrate to colloid, 200g ethyl acetate is added, chlorination is added dropwise under cooling condition
System is concentrated into half, solid is precipitated, dries to obtain Beta-alanine by the ethyl acetate solution of hydrogen until pH stops being added dropwise after being 3
Methyl ester hydrochloride 192g, measuring purity is 99.1%, continues to be concentrated, obtains Beta-alanine methyl ester hydrochloride 68g, measuring purity is
98.6%, calculating methyl cyanoacetate conversion ratio is 95.7%.
Claims (9)
1. a kind of preparation method of Beta-alanine ester type compound, includes the following steps:
A) cyanoacetate is dissolved in solvent I, alkaline matter is added and Raney's nickel carries out catalytic hydrogenation reaction, after reaction
It filters and filtrate is concentrated, obtain product A；
B) product A is dissolved in solvent II, II solution of solvent of hydrogen chloride is added dropwise, after system pH is 2~3, stop drop
Add, obtains mixed liquid B；
C) mixed liquid B is concentrated, is dried under reduced pressure, obtain target product.
2. the preparation method of Beta-alanine ester type compound according to claim 1, it is characterised in that: in the step a),
The pressure of hydrogenation reaction is 2-8Mpa, and temperature is 30-70 DEG C, reaction time 2-10h.
3. the preparation method of Beta-alanine ester type compound according to claim 1, it is characterised in that: in the step a),
Cyanoacetate is one of methyl cyanoacetate, ethyl cyanoacetate, the cyanoacetic acid tert-butyl ester.
4. the preparation method of Beta-alanine ester type compound according to claim 1, it is characterised in that: in the step a),
Solvent I is one of methanol, ethyl alcohol, ethyl acetate, methyl formate.
5. the preparation method of Beta-alanine ester type compound according to claim 1, it is characterised in that: in the step a),
The mass ratio of cyanoacetate and solvent I is 1:(3~10).
6. the preparation method of Beta-alanine ester type compound according to claim 1, it is characterised in that: in the step a),
Alkaline matter is one of potassium hydroxide, sodium hydroxide, potassium carbonate, ammonia, sodium acetate, sodium formate, sodium methoxide, sodium ethoxide.
7. the preparation method of Beta-alanine ester type compound according to claim 1, it is characterised in that: in the step a),
The additive amount of alkaline matter is the 5%~20% of cyanoacetate quality.
8. the preparation method of Beta-alanine ester type compound according to claim 1, it is characterised in that: in the step a),
The additive amount of Raney's nickel is the 5%~20% of cyanoacetate quality.
9. the preparation method of Beta-alanine ester type compound according to claim 1, it is characterised in that: in the step b),
Solvent II is one of methanol, ethyl alcohol, ethyl acetate, isopropanol.
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| CN201910353559.5A CN109970585A (en) | 2019-04-29 | 2019-04-29 | A kind of preparation method of Beta-alanine ester type compound |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115322082A (en) * | 2022-08-31 | 2022-11-11 | 郑州药领医药科技有限公司 | Preparation method of tetralone compound |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000086599A (en) * | 1998-09-17 | 2000-03-28 | Lion Corp | PREPARATION OF N-SUBSTITUTED-beta-ALANINE OR ITS SALT AND SURFACTANT COMPOSITION INCLUDING THE SAME |
| CN1329595A (en) * | 1998-10-12 | 2002-01-02 | 藤泽药品工业株式会社 | New processes for producing beta-alanine derivative |
| CN105367435A (en) * | 2015-12-03 | 2016-03-02 | 张伟 | Preparation method for beta-alanine t-butyl ester hydrochloride |
-
2019
- 2019-04-29 CN CN201910353559.5A patent/CN109970585A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2000086599A (en) * | 1998-09-17 | 2000-03-28 | Lion Corp | PREPARATION OF N-SUBSTITUTED-beta-ALANINE OR ITS SALT AND SURFACTANT COMPOSITION INCLUDING THE SAME |
| CN1329595A (en) * | 1998-10-12 | 2002-01-02 | 藤泽药品工业株式会社 | New processes for producing beta-alanine derivative |
| CN105367435A (en) * | 2015-12-03 | 2016-03-02 | 张伟 | Preparation method for beta-alanine t-butyl ester hydrochloride |
Non-Patent Citations (2)
| Title |
|---|
| PRABHAKAR Y.，等: "Ultrasonic assisted synthesis of methyl esters of carboxylic acids by using most convenient, safe and cost effecting reagent NaHSO4", 《PHARMA CHEMICA》 * |
| 韩秋敏，等: "β-氨基酸乙酯盐酸盐的合成与表征", 《广州化工》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115322082A (en) * | 2022-08-31 | 2022-11-11 | 郑州药领医药科技有限公司 | Preparation method of tetralone compound |
| CN115322082B (en) * | 2022-08-31 | 2024-02-23 | 郑州药领医药科技有限公司 | Preparation method of tetralone compound |
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Application publication date: 20190705 |