Method for synthesizing intermediate L-2-aminobutyrylamide hydrochloride of chiral drug levetiracetam

A technology of aminobutanamide and chiral drugs, which is applied in the field of preparation of chiral drug intermediates, can solve the problems of safety, three-waste treatment and high environmental protection requirements, long reaction steps, influence on process safety and the like

Inactive Publication Date: 2011-04-20
浙江沙星医药化工有限公司
View PDF4 Cites 25 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the route has few steps, the starting material L-2-aminobutyric acid is expensive and the cost is higher
The second is to use n-propionaldehyde as the starting material to prepare the target compound through six steps of Streck reaction, hydrolysis, resolution, esterification, ammonolysis and cyclization. This method has long reaction steps and the yield is only 4.7%. , CN1583721A improved this route, using iso-n-propanal and sodium cyanide as starting materials, and prepared the target compound through four steps of Streck reaction, hydrolysis, resolution and cyclization. With this method, the yield of the product It has been improved, but this method uses the highly toxic compound sodium cyanide, which has higher requirements on the safety

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for synthesizing intermediate L-2-aminobutyrylamide hydrochloride of chiral drug levetiracetam
  • Method for synthesizing intermediate L-2-aminobutyrylamide hydrochloride of chiral drug levetiracetam
  • Method for synthesizing intermediate L-2-aminobutyrylamide hydrochloride of chiral drug levetiracetam

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] In a 1000ml reaction flask, add 83.5g of 2-bromobutyric acid, 125g of 28% ammonia water and 500ml of diethyl ether, cool down to -5°C, slowly add 59.5g of thionyl chloride dropwise under stirring, keep stirring and react after dropping 10 hours. After the reaction, the layers were separated, the organic layer was washed with water, and concentrated to dryness to obtain 73 g of white solid 2-bromobutyramide with a yield of 88% and a purity of 98.5%.

Embodiment 2

[0027] In a 2000ml reaction flask, add 167g of 2-bromobutyric acid, 250g of 28% ammonia water and 1000ml of methyl tert-butyl ether, cool down to 0°C, slowly add 119g of thionyl chloride dropwise under stirring, and naturally The temperature was raised to 20°C, and the reaction was carried out under heat preservation and stirring for 2 hours. After the reaction was complete, the layers were separated, the organic layer was washed with water, and concentrated to dryness to obtain 143 g of white solid 2-bromobutyramide with a yield of 86% and a purity of 98.9%.

Embodiment 3

[0029] In a 2000ml reaction flask, add 167g of 2-bromobutyric acid, 250g of 28% ammonia water and 1000ml of methyl tert-butyl ether, cool down to 0°C, slowly add 119g of thionyl chloride dropwise under stirring, and naturally Raise the temperature to 10°C, heat and stir for 4 hours. After the reaction was complete, the layers were separated, the organic layer was washed with water, and concentrated to dryness to obtain 148 g of white solid 2-bromobutyramide, with a yield of 89.2% and a purity of 99.2%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention belongs to the field of the preparation of chiral drug intermediates and particularly relates to a method for synthesizing a intermediate L-2-aminobutyrylamide hydrochloride of chiral drug levetiracetam. The method is characterized by taking 2-bromobutyric acid as a starting raw material and comprising the steps of: firstly, preparing a 2-bromobutyric amide intermediate, reacting the 2-bromobutyric amide intermediate to generate DL-2-aminobutyrylamide, and finally, splitting and salifying the DL-2-aminobutyrylamide to synthesize the L-2-aminobutyrylamide hydrochloride. Compared with the traditional synthesis method, the method has the advantages of mild reaction conditions, low cost, higher yield, greatly improved process safety, cheap and easily-obtained raw materials, simple unit operations and low requirements on equipment and is suitable for industrial large-scale production, amidation reaction is carried out at normal temperature and normal pressure, and the reaction is easy to control.

Description

technical field [0001] The invention belongs to the field of preparation of chiral drug intermediates, in particular to a method for synthesizing L-2-aminobutyramide hydrochloride, an intermediate of chiral drug levetiracetam. Background technique [0002] The preparation method of chiral drug levetiracetam has been reported in the literature, such as EP1566376, CN1015541B and CN1583721A have introduced the synthesis of the compound respectively, the main route has, the first is starting raw material with L-2-aminobutyric acid, through Esterification, ammonolysis, cyclization or cyclization, esterification, and then ammonolysis to obtain the target product. Although this route has few steps, the starting material L-2-aminobutyric acid is expensive and the cost is higher. The second is to use n-propionaldehyde as the starting material to prepare the target compound through six steps of Streck reaction, hydrolysis, resolution, esterification, ammonolysis and cyclization. This...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07C237/06C07C231/20
Inventor 黄小庭唐治文蒋苗丹
Owner 浙江沙星医药化工有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap