A kind of preparation method of 3-aminobutanamide compound

An aminobutyramide and compound technology, which is applied in the field of preparation of 3-aminobutanamide compounds, can solve the problems that liquid ammonia cannot be directly recovered and recycled, is not suitable for industrial production, requires high pressure and the like, and achieves easy operation and environmental protection. Friendly, mild reaction conditions

Active Publication Date: 2019-10-18
ZHEJIANG UNIV OF TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] Fernelius, W.Conard and Bowman, Glade B. et al. reported that crotonic acid Methyl ester is used as a raw material in liquid ammonia for ammonolysis to prepare 3-aminobutyramide. This method needs to be carried out under liquid ammonia and requires high pressure. Excess liquid ammonia cannot be directly recovered and recycled.
[0006] In their research on EGFR inhibitors (Eur.J.Med.Chem., 119,278-299; 2016), Jin Han, Svein Jacob Kaspersen et al. reported that 3-aminophenylpropionic acid was used as a raw material and sulfuric acid was used as a catalyst After esterification with methanol to generate 3-aminophenylpropionate methyl ester, ammonolysis in ammonia water to prepare 3-aminophenylpropionamide, this method will produce a large amount of waste acid, which is not friendly to the environment and is not suitable for industrial production

Method used

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  • A kind of preparation method of 3-aminobutanamide compound
  • A kind of preparation method of 3-aminobutanamide compound
  • A kind of preparation method of 3-aminobutanamide compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] (1) Add 37.5% (mass fraction) ammoniacal liquor (91g, 2.00mol) in the 250mL four-necked round bottom flask that is equipped with mechanical stirring, 3-oxobutanoic acid methyl ester (11.6 mol) shown in formula (I-1) g, 0.10mol), react at 30°C, and after liquid chromatography detects that the reaction is complete, filter the reaction solution, and the filtrate can be directly applied to the next batch, and the resulting filter cake is soaked with water for 2 to 3 times, and placed in an oven at 50 After drying at ~60°C, 8.65 g of 3-aminobutenamide represented by formula (II-1) was obtained. The purity by liquid chromatography was 98.2%, and the yield was 84.8%. The detection condition of liquid chromatography is: C18 column, and the mobile phase volume ratio is: acetonitrile: water = 60:40.

[0027] (2) In a 250mL autoclave equipped with mechanical stirring, add 100mL of methanol, 3-aminobutenamide (8.16g, 0.08mol) shown in formula (II-1), 0.4g of Raney nickel, and feed ...

Embodiment 2

[0030] (1) Add 25.0% (mass fraction) ammoniacal liquor (149g, 2.20mol) in the 250mL four-neck round bottom flask that is equipped with mechanical stirring, 3-oxobutanoic acid ethyl ester (13.0 mol) shown in formula (I-2) g, 0.10mol), react at 40°C, and after liquid chromatography detects that the reaction is complete, filter the reaction solution, and the filtrate can be directly applied to the next batch, and the resulting filter cake is soaked with water for 2 to 3 times, and placed in an oven at 50 After drying at ~60°C, 8.55 g of 3-aminobutenamide represented by formula (II-2) was obtained, with a purity of 98.2% as detected by liquid chromatography. Yield 83.8%.

[0031] (2) In a 250mL autoclave equipped with mechanical stirring, add 100mL of methanol, 3-aminobutenamide (8.16g, 0.08mol) shown in formula (II-2), 0.4g of Raney nickel, feed H 2 , keep the pressure 0.5MPa, react under the condition of 40 DEG C, after liquid chromatography detects that the reaction is complet...

Embodiment 3

[0034] (1) Add 37.5% (mass fraction) ammoniacal liquor (136g, 3.00mol) in the 250mL four-necked round bottom flask that is equipped with mechanical stirring, 3-oxophenylbutyric acid ethyl ester shown in formula (I-3) ( 20.6g, 0.10mol), and reacted at 35°C. After the reaction was detected by liquid chromatography, filter the reaction solution. The filtrate can be directly applied to the next batch. The obtained filter cake was soaked with water for 2 to 3 times, and placed in an oven at After drying at 50-60°C, 14.04 g of 3-aminophenylbutenamide represented by the formula (II-3) was obtained, the purity by liquid chromatography was 98.5%, and the yield was 79.8%.

[0035] (2) In a 250mL autoclave equipped with mechanical stirring, add 150mL of methanol, 3-aminophenylbutenamide (12.32g, 0.07mol) shown in formula (II-3), 1.2g of Raney nickel, feed H 2 , keep the pressure 0.5MPa, react under the condition of 45 DEG C, after the liquid chromatography detects that the reaction is co...

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Abstract

The invention discloses a preparation method of a 3-aminobutyramide type compound. The preparation method includes the following steps: 1) performing a reaction to a compound (I) as a raw material in ammonia water at 20-70 DEG C to produce a compound (II) after the reaction is completed; 2) adding the compound (II) to a solvent, and performing a reductive hydrogenation reaction at 30-50 DEG C under 0.1-1.5 MPa to produce a compound (III), Raney nickel being a catalyst. The preparation method is simple in processes and has gentle conditions and is composed of common ammonolysis reaction and hydrogenation reduction reaction (ammonolysis reactions in the prior art require high-pressure equipment and are high in energy consumption), wherein an ammonolysis mother liquid can be directly recycled, so that the preparation method has simple operations. The product is high in yield and purity, wherein total yield is more than 77% and purity is more than 98%. The method is suitable for industrial production of the 3-aminobutyramide type compound and is environment-friendly.

Description

[0001] (1) Technical field [0002] The invention relates to a preparation method of 3-aminobutanamide compounds. [0003] (2) Background technology [0004] 3-Aminobutyramides are important intermediates in organic synthesis and are widely used in pesticides and medicines. It is of great practical significance to study its synthesis and develop a process route suitable for industrial production. [0005] Fernelius, W.Conard and Bowman, Glade B. et al. reported that crotonic acid Methyl ester is used as a raw material in liquid ammonia for ammonolysis to prepare 3-aminobutyramide. This method needs to be carried out under liquid ammonia and requires relatively high pressure. Excess liquid ammonia cannot be directly recovered and recycled. [0006] In their research on EGFR inhibitors (Eur.J.Med.Chem., 119, 278-299; 2016), Jin Han, Svein Jacob Kaspersen and others reported that 3-aminophenylpropionic acid was used as a raw material and sulfuric acid was used as a catalyst Aft...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C231/12C07C237/06C07C237/20
Inventor 丁成荣裘志炜张国富吕井辉王兴飞季方良
Owner ZHEJIANG UNIV OF TECH
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