Synthesis method of S-2-aminobutanamide hydrochloride

Abstract

The invention discloses a synthesis method of S-2-aminobutanamide hydrochloride, which comprises the following steps of: 1) ammoniation: respectively carrying out ammoniation on methyl 2-bromobutyrate in a methanol-ammonia solution and anhydrous isopropyl alcohol so as to generate DL-2-aminobutanamide; 2) resolving: combining the DL-2-aminobutanamide with an L-tartaric acid to carry out salting-out, and carrying out resolution and purification on the obtained product; and 3) releasing and salifying: directly feeding hydrogen chloride into a crude product subjected to resolution and purification so as to carry out releasing and salifying, thereby obtaining S-2-aminobutanamide hydrochloride with optical activity. The method disclosed by the invention is cheap and easily obtained in raw materials, simple in operation, mild in conditions, high in process safety, low in equipment requirement, and easy to realize industrialized large-scale production.

Description

technical field [0001] The invention relates to the field of organic chemical synthesis and preparation, in particular to a method for synthesizing S-2-aminobutyramide hydrochloride. Background technique [0002] The chemical name of the chiral drug levetiracetam is (S)-α-ethyl-2-oxo-1-pyrrolidineacetamide, and its preparation method has been reported in literature, such as CN1015541B, EP1566376 and CN1583721A. 2-aminobutyramide hydrochloride is an important intermediate of levetiracetam, and there are many patent documents such as WO2006 / 095362 and US2007 / 087924 that report the use of 2-aminobutanamide hydrochloride to synthesize levetiracetam Tan, so 2-aminobutyramide hydrochloride in levetiracetam. The main methods of chemically synthesizing 2-aminobutyramide hydrochloride are as follows: 1) Using butyric acid as a starting material, 2-aminobutyramide is obtained through bromination, methylation, ammoniation and acidification steps, and finally the acid is adjusted to ob...

AI Technical Summary

Problems solved by technology

This method requires four-step reactions, and uses bromine as an environmentally unfriendly raw material. The amination process needs to be carried out under high pressure, which is not conducive to industrialization, while increasing production costs and bringing safety hazards to production; 2) using 2-amino Butyric acid is used as a raw material, and this product is obtained through chlorination, ammoniation, and acidification of thionyl chloride. This method uses thionyl chloride. Although the hydrogen chloride produced by thionyl chloride can be absorbed and discharged by lye, the absorption effect of sulfur dioxide Poor, sulfur-containing waste water is relatively polluting to the environment, and the relevant state departments have clearly stipulated that these toxic and harmful reagents that seriously pollute the environment must be gradually replaced; 3) Use 2-bromobutyric acid to prepare 2-aminobutyric acid Acid, then methyl esterification to prepare 2-aminobutyric acid methyl ester, then amidation synthesis route, and then through resolution, after resolution, use sodium hydroxide or ammonia water to release and then form a salt to obtain the product, so obtained The product will not be very high in terms of yield, the main reason is that the steps are relatively long and the process is complicated, resulting in the problem of low product yield

Images