CN112209844A - Synthetic method of 3-methylamino propionic acid - Google Patents
Synthetic method of 3-methylamino propionic acid Download PDFInfo
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- CN112209844A CN112209844A CN202011136398.3A CN202011136398A CN112209844A CN 112209844 A CN112209844 A CN 112209844A CN 202011136398 A CN202011136398 A CN 202011136398A CN 112209844 A CN112209844 A CN 112209844A
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- China
- Prior art keywords
- propionic acid
- compound
- methylamino
- synthesizing
- methylamino propionic
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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
- C07C227/16—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 not involving the amino or carboxyl groups
-
- 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
- C07C227/06—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid
- C07C227/08—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid by reaction of ammonia or amines with acids containing functional groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a synthetic method of 3-methylamino propionic acid. Mainly solves the technical problems that the reaction steps for preparing the 3-methylamino propionic acid are more and the scale-up production is not easy to realize at present. The synthesis method comprises the following steps: in ethanol solution, acrylic acid reacts with N-methylbenzylamine to generate a compound 1; the compound 1 is subjected to normal pressure hydrogenation debenzylation under the catalysis of 10% palladium-carbon to generate a target compound 2. As a medical intermediate, 3-methylamino propionic acid is widely used for synthesizing other amino acid derivatives and polypeptide active substances and synthesizing hapten for high-sensitivity and quick enzyme-linked immunosorbent assay aiming at pesticide residues.
Description
Technical Field
The invention relates to a method for synthesizing 3-methylamino propionic acid (CAS: 2679-14-3). As a medical intermediate, 3-methylamino propionic acid is widely used for synthesizing other amino acid derivatives and polypeptide active substances and synthesizing hapten for high-sensitivity and quick enzyme-linked immunosorbent assay aiming at pesticide residues.
Background
Since 1960, the aryl urea herbicide series of meturon, diuron and linuron are widely applied in agriculture, and can selectively inhibit broad-leaf weeds in crops such as grains, fruits and the like only by using a low dosage in the early stage of seed germination and after emergence of seedlings to before maturity. 3-Methylaminopropionic acid was used for the synthesis of hapten 3: (J. Agric. Food Chem.1994, 42413-422) for high sensitivity and rapid enzyme-linked immunosorbent assay for pesticide residues:
3-methylamino propionic acid as amino acid derivative is also widely used in the synthesis of polypeptide active matter, such as new cyclic peptide series product extracted from ocean sponge of Indonesia (Tetrahedron 56 (2000) 9079-9092).
The synthesis methods reported at present are all multistep reactions, and the raw materials such as halide, amine and the like are needed, so the odor is large, and the amplification production is not facilitated.
Disclosure of Invention
The invention mainly aims to provide a method for synthesizing 3-methylamino propionic acid. Mainly solves the technical problems that the reaction steps for preparing the 3-methylamino propionic acid are more and the scale-up production is not easy to realize at present.
The technical scheme of the invention is as follows: a synthetic method of 3-methylamino propionic acid is characterized by comprising the following steps: firstly, in an ethanol solution, reacting acrylic acid with N-methylbenzylamine to generate a compound 1; secondly, the compound 1 is subjected to normal pressure hydrogenation debenzylation under the catalysis of palladium-carbon to generate a crude product of a target compound 2. The synthesis route is as follows:
the first step reaction is stirred for 3 hours at 65 ℃; the second step of normal pressure hydrogenation debenzylation reaction is carried out under the catalysis of 10 percent palladium-carbon (the weight percentage of palladium is 10 percent); and recrystallizing the crude reaction product in acetone for purification.
The invention has the beneficial effects that: the invention relates to a method for synthesizing 3-methylamino propionic acid by using acrylic acid and N-methylbenzylamine as raw materials through hydrogenation and debenzylation. The reaction raw materials are cheap, the intermediate product 1 does not need to be separated after the first step of reaction is finished, palladium-carbon is directly added into an ethanol solution for normal-pressure hydrogenation debenzylation, and the method is simple in post-treatment, high in yield and very suitable for the large-scale production of 3-methylamino propionic acid.
Detailed Description
Step 1:
ethanol (8L), acrylic acid (1.6 kg, 22.2 mol) and N-methylbenzylamine (4.0 kg, 33.0 mol) were charged to a 20L reactor, heated to 65 deg.C, stirred for 3 hours, then cooled to room temperature, and stirred overnight. LC-MS (ESI) M/z 194.15 [ M + H [ ]]+。
Step 2:
10% palladium carbon was added, hydrogen was introduced under normal pressure, and the mixture was stirred at room temperature overnight. The reaction was filtered, palladium on charcoal was recovered, the filtrate was concentrated at 50 ℃ to remove ethanol, acetone (8L) was added, stirred at room temperature for 3 hours, the resulting solid was filtered and dried at 50 ℃ to give the title compound 2 (2.1 kg, 20.2 mol, 92%) as a white solid.1H NMR (400 MHz, D2O) 3.16 (t, J = 6.4 Hz, 2H), 2.69 (s, 3H), 2.53 (t, J = 6.4 Hz, 2H)；LC-MS (ESI): m/z 104.08 [M+H]+。
Claims (3)
1. A synthetic method of 3-methylamino propionic acid is characterized in that: the method comprises the following steps: firstly, in an ethanol solution, reacting acrylic acid with N-methylbenzylamine to generate a compound 1; secondly, the compound 1 is subjected to normal pressure hydrogenation debenzylation under the catalysis of palladium-carbon to generate a crude product of a target compound 2; the synthesis route is as follows:
2. the method for synthesizing 3-methylamino propionic acid as claimed in claim 1, wherein: the first reaction step was carried out at 65 ℃ for 3 hours by reacting acrylic acid with N-methylbenzylamine.
3. The method for synthesizing 3-methylamino propionic acid as claimed in claim 1, wherein: and recrystallizing the crude reaction product in the second step by using acetone.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011136398.3A CN112209844A (en) | 2020-10-22 | 2020-10-22 | Synthetic method of 3-methylamino propionic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011136398.3A CN112209844A (en) | 2020-10-22 | 2020-10-22 | Synthetic method of 3-methylamino propionic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112209844A true CN112209844A (en) | 2021-01-12 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011136398.3A Pending CN112209844A (en) | 2020-10-22 | 2020-10-22 | Synthetic method of 3-methylamino propionic acid |
Country Status (1)
| Country | Link |
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| CN (1) | CN112209844A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101686982A (en) * | 2007-05-10 | 2010-03-31 | Amr科技公司 | The purposes of the tetrahydro benzo azepine that aryloxy group and heteroaryloxy replace and blocking-up norepinephrine, dopamine and 5-hydroxy tryptamine reuptake |
| CN107382761A (en) * | 2017-08-07 | 2017-11-24 | 滨海吉尔多肽有限公司 | The synthetic method that a kind of 3 amino 3 (4 hydroxy phenyl) propionic acid are split |
| US20190119200A1 (en) * | 2016-04-06 | 2019-04-25 | Abbvie Inc. | Tertiary amides and method of use |
-
2020
- 2020-10-22 CN CN202011136398.3A patent/CN112209844A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101686982A (en) * | 2007-05-10 | 2010-03-31 | Amr科技公司 | The purposes of the tetrahydro benzo azepine that aryloxy group and heteroaryloxy replace and blocking-up norepinephrine, dopamine and 5-hydroxy tryptamine reuptake |
| US20190119200A1 (en) * | 2016-04-06 | 2019-04-25 | Abbvie Inc. | Tertiary amides and method of use |
| CN107382761A (en) * | 2017-08-07 | 2017-11-24 | 滨海吉尔多肽有限公司 | The synthetic method that a kind of 3 amino 3 (4 hydroxy phenyl) propionic acid are split |
Non-Patent Citations (1)
| Title |
|---|
| 刘鹰翔: "《药物合成反应》", 31 August 2017, 中国中医药出版社 * |
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Application publication date: 20210112 |
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| RJ01 | Rejection of invention patent application after publication |