Preparation method of (R,S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide

A technology of pyrrolidine acetamide and oxo substitution, which is applied in the direction of organic chemistry, can solve the problems of high cost, large amount of solvent, and difficult recovery, etc., and achieve the effects of improved service life, short reaction cycle, and easy operation

Inactive Publication Date: 2012-09-26
TIANJIN JIUHAI MEDICAL TECH
View PDF1 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The preparation method of (s)-oxiracetam in the patent WO2005 / 115978, wherein (S)-4-chloro-3-hydroxybutyrate and glycinamide react under alkaline conditions to obtain the final product oxiracetam , but due to the high cost of (S)-4-chloro-3-hydroxybutyrate, this directly affects the cost of oxiracetam
Make (s)-oxiracetam difficult to popularize
[0004] In addition, in the preparation method of (s)-oxiracetam in the patent WO2005 / 115978, the reaction can be carried out at a temperature of 0-100°C, but in such a wide temperature range, the efficiency of the reaction varies greatly , it still cannot give a reaction temperature range with the highest product yield
[0005] In addition, the silica gel column chromatography method is adopted in the purification of the final product oxiracetam, and the eluent used is an organic mixed solvent. The amount of solvent is large, the pollution is large and difficult to recycle, the cost is high, and the silica gel column chromatography method is not suitable. Industrial production

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
  • Preparation method of (R,S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide
  • Preparation method of (R,S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide
  • Preparation method of (R,S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] A kind of preparation method of (R, S)-4-hydroxyl-2-oxo-1-pyrrolidineacetamide, its concrete steps are:

[0056] (a) 55.0g of glycinamide hydrochloride, 29.2g of sodium carbonate, 99.6g of (R, S)-4-chloro-3-hydroxybutyric acid ethyl ester, and 500ml of absolute ethanol are dropped into the reaction flask During the process, the reaction was heated to reflux for 23 hours, and then the reaction vessel was sealed to raise the internal temperature to 90° C. and kept for 1 hour to terminate the reaction. After cooling to 60°C, filter with suction, concentrate the mother liquor to nearly dryness, add 40 ml of methanol for beating and filter, then use 90 ml of ethanol for beating at 60°C for 1 hour, cool to room temperature, and filter to obtain (R,S)-4-hydroxy-2 - crude product 37g of oxo-1-pyrrolidineacetamide;

[0057] (d) The above crude product was dissolved in 370ml of water, treated with 120g of Pleinlight 732 strong acidic styrene-based cation exchange resin, and the ...

Embodiment 2

[0060] A kind of preparation method of (R, S)-4-hydroxyl-2-oxo-1-pyrrolidineacetamide, its concrete steps are:

[0061] (a) 55.0g of glycinamide hydrochloride, 29.2g of sodium carbonate, 99.6g of (R, S)-4-chloro-3-hydroxybutyric acid ethyl ester, and 500ml of absolute ethanol are dropped into the reaction flask During the process, heat to reflux for 24 hours, then cool the inner temperature of the reaction vessel to 60°C and filter with suction, concentrate the mother liquor to nearly dryness, add 40 ml of methanol for beating and filtering, and then use 90 ml of ethanol to beat the crude product at 60°C 1h, after cooling to room temperature, filtered to obtain 32g of crude product of (R,S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide;

[0062] (d) The above crude product was dissolved in 370ml of water, treated with 120g of Pleinlight 732 strong acidic styrene-based cation exchange resin, and the product part was collected. Neutralize and collect the aqueous solution obtained with...

Embodiment 3

[0065] A kind of preparation method of (R, S)-4-hydroxyl-2-oxo-1-pyrrolidineacetamide, its concrete steps are:

[0066] (a) 55.0g of glycinamide hydrochloride, 29.2g of sodium carbonate, 99.6g of (R, S)-4-chloro-3-hydroxybutyric acid ethyl ester, and 500ml of absolute ethanol are dropped into the reaction flask During the process, the reaction was heated to reflux for 28 hours, and then the reaction vessel was sealed to raise the internal temperature to 90° C. and kept for 1 hour to terminate the reaction. After cooling to 60°C, filter with suction, concentrate the mother liquor to nearly dryness, add 40 ml of methanol for beating and filter, then use 90 ml of ethanol for beating at 60°C for 1 hour, cool to room temperature, and filter to obtain (R,S)-4-hydroxy-2 - crude product 32g of oxo-1-pyrrolidineacetamide;

[0067] (d) The above crude product was dissolved in 370ml of water, treated with 120g of Pleinlight 732 strong acidic styrene-based cation exchange resin, and the ...

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 provides a preparation method of (R,S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide. The preparation method comprises that (R,S)-4-halogeno-3-hydroxybutyrate as a raw material undergoes a reaction in the presence of one or more polar solvents under alkaline conditions to produce a crude product of (R,S)-4-hydroxy-2-oxo-1-pyrrolidinylacetamide and the crude product of (R,S)-4-hydroxy-2-oxo-1-pyrrolidinylacetamide is purified. The preparation method is characterized in that through using an inorganic base of which molar weight is 1 to 1.2 times molar weight of glycinamide hydrochloride in the reaction under alkaline conditions in batches or at one time, the alkaline conditions for keeping the reaction can be controlled so that the reaction is fully and unnecessary waste caused by the large excess of the inorganic base is prevented; and when a target product of (R,S)-4-hydroxy-2-oxo-1-pyrrolidineacetamide ((R,S)-oxiracetam) produced by a reflux reaction in one or more polar solvents under ordinary pressure has the maximum concentration, the reaction is stopped or is blocked and then continues at a temperature of 90 DEG C for 1 hour. Through pressurization, a reaction yield is improved by about 15% and a cost is greatly reduced.

Description

technical field [0001] The present invention relates to a preparation method of (R, S)-4-hydroxyl-2-oxo-1-pyrrolidineacetamide (commercial name is oxiracetam, the same below). Background technique [0002] Olaci is a nootropic drug synthesized for the first time in 1974 by the Italian Shi Kebichem Company, which is composed of two isomers (s)-oxiracetam (s)-oxiracetam and (R)-ola A racemate composed of oxiracetam. [0003] The preparation method of (s)-oxiracetam in the patent WO2005 / 115978, wherein (S)-4-chloro-3-hydroxybutyrate and glycinamide react under alkaline conditions to obtain the final product oxiracetam , but due to the high cost of (S)-4-chloro-3-hydroxybutyrate, this directly affects the cost of oxiracetam. Make (s)-oxiracetam difficult to popularize. [0004] In addition, in the preparation method of (s)-oxiracetam in the patent WO2005 / 115978, the reaction can be carried out at a temperature of 0-100°C, but in such a wide temperature range, the efficiency o...

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): C07D207/273
Inventor 杨卫民
Owner TIANJIN JIUHAI MEDICAL TECH
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