Preparation method for 2-(2-oxo-pyrrolidyl) butanamide

Abstract

A preparation method for 2-(2-oxo-pyrrolidyl) butanamide belongs to the technical field of fine chemical synthesis, and includes the steps: leading 2-pyrrolidone serving as raw materials with sodium ethylate, alpha-bromo-ethyl butyrate, liquid caustic soda, acylation reagent, ammonia and the like respectively to sequentially undergo substitution, hydrolysis, acylation, ammoniation and the like to obtain the target product, namely, 2-(2-oxo-pyrrolidyl) butanamide. The method adopting the technology is simple and available in raw materials, mild in reaction conditions, low in requirements on equipment, convenient in equipment operation, short in reaction route and high in reaction yield, the prepared 2-(2-oxo-pyrrolidyl) butanamide is high in purity, the total yield is higher than 68.1%, purity is higher than 99.2%, and the method is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of fine chemical synthesis, and in particular relates to a synthesis method of 2-(2-oxopyrrolidinyl)butyramide. technical background [0002] Levetiracetam chemical name (S)-α-ethyl-2-oxo-1-pyrrolidineacetamide, S-enantiomer of 2-(2-oxopyrrolidinyl)butyramide Construct. It is a nootropic drug developed by the Belgian Union Chemical Company (UCB), which was first launched in the United States in April 2000 and is an effective antiepileptic drug. [0003] At present, Etiracetam can be synthesized by the following processes: 1) Using 2-pyrrolidone as raw material, reacting with NaH under the action of phase transfer catalyst triethylbenzyl ammonium chloride (TEBA) to form sodium salt, and then reacting with α- Methyl bromobutyrate is reacted to generate methyl α-ethyl-2-oxo-1-pyrrolidine butyrate, and then directly aminated to obtain the target product {Synthetic Chemistry, 2005 (13), 91-92}, this method Sod...

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Problems solved by technology

[0003] At present, Etiracetam can be synthesized by the following processes: 1) Using 2-pyrrolidone as raw material, reacting with NaH under the action of phase transfer catalyst triethylbenzyl ammonium chloride (TEBA) to form sodium salt, and then reacting with α- Methyl bromobutyrate is reacted to generate methyl α-ethyl-2-oxo-1-pyrrolidine butyrate, and then directly aminated to obtain the target product {Synthetic Chemistry, 2005 (13), 91-92}, this method Sodium hydride is used in the production process, and hydrogen gas is generated during the production process, which brings production safety hazards to the production; 2) α-ethyl-2-oxo-1-pyrrolidine butyric acid and alkyl haloformate are stored at -30°C~- React in dichloromethane at 40°C, and then pass ammonia gas to obtain the target product, or by the general formula XCH 2 CH 2 CONHCH (CH 2 CH 3 )CONH 2 (US4943639), the price of raw materials in this method is expensive and the cost is high; 3) L-methionine is used as raw material, after esterification, ammonolysis, and reaction with methyl 4-chlorobutyrate The product (GB: 2225322) was obtained by demethylthiolation of nickel nickel. This method has long steps and low yield, which is not conducive to industrial production; Levetiracetam (CN1583721) was produced in four steps of splitting and cyclization. In this method, the highly toxic sodium cyanide was used, and the wastewater treatment requirements in the production process were high.

[0004] In the above-mentioned synthesis process of etiracetam, there are mainly problems such as high cost of raw materials, harsh reaction conditions, high equipment requirements, and low total yield, which are not suitable for industrial application