Preparation method of (S)-(+)-2-aminobutanamide hydrochloride

Abstract

The invention discloses a synthetic process of a chiral drug (S)-alpha-ethyl-2-oxo-pyrrolidine acetamide (levetiracetam) intermediate (S)-(+)-2-aminobutanamide hydrochloride which has anti-epileptic function. The synthetic process comprises the following steps: performing condensation on acetone cyanohydrins and n-propanal as initial raw materials in the presence of a catalyst to obtain 2-hydroxybutyronitrile; then carrying out a reaction with ammonia to obtain 2-amino butyronitrile; then carrying out hydrolysis to obtain 2-aminobutanamide; then splitting and salifying the 2-aminobutanamide to obtain a target product. The synthetic process is high in yield, the raw materials are low in price and are easily purchased on a large scale, and the synthetic process overcomes the defects that several existing processes need highly toxic and highly polluting raw materials and is simple in process operation and low in cost. Mother liquor after splitting is further racemized and split and is recycled repeatedly, so that the synthetic process is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and relates to a synthesis, resolution and racemization of a chiral drug levetiracetam intermediate (S)-(+)-2-aminobutyramide hydrochloride. Background technique [0002] The synthesis of the chiral drug levetiracetam intermediate (S)-(+)-2-aminobutyramide hydrochloride has been reported in a large number of documents, and its main synthetic routes are as follows, one is reported in WO2010019469 as L -2-aminobutyric acid is used as the starting material to obtain the target compound through esterification, aminolysis, and salt formation. Although this method has a short route, the starting material L-2-aminobutyric acid is expensive, and the esterification reagent chlorinated chlorinated Sulfone is highly polluting to the environment. The 2nd, CN1583321A report takes n-propionaldehyde, sodium cyanide as starting material to obtain target product through Stigrey condensa...

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Problems solved by technology

The 3rd, CN101130504A report takes 2-bromobutyric acid as starting raw material, obtains target compound through amination, esterification, ammonolysis, resolution, salification, and the used raw material 2-bromobutyric acid of this method is equally expensive Expensive, low reactive atom economy

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