A kind of preparation method of 3-aminobutanamide compound

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...

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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

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