Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Method for purifying levetiracetam crude product

A purification method and a crude product technology are applied in the field of purification of levetiracetam crude products, can solve the problems of large usage, low yield of levetiracetam, low product purity, etc., achieve cost reduction, less solvent consumption, good solubility

Inactive Publication Date: 2014-07-16
SUZHOU TIANMA SPECIALTY CHEM
View PDF11 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The object of the invention is to provide a kind of purification method of levetiracetam crude product, solves existing in the prior art in purifying levetiracetam crude product process and uses a large amount of organic solvents, yield is lower and levetiracetam The problem of low product purity

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 purifying levetiracetam crude product

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Embodiment one: a kind of purification method of levetiracetam crude product

[0025] The purification method consists of the following steps in turn:

[0026] In the first step, the crude product of levetiracetam is added to the crystallization system, and the weight ratio of the crystal system to the crude product of levetiracetam is 1~10:1; wherein, the crystallization system is C3~C6 ketones and A mixed system of purified water, the weight ratio of the C3~C6 ketones to the purified water is 10~50:1;

[0027] In the second step, the system obtained in the first step is heated and dissolved, and the dissolution temperature is 50-90° C.;

[0028] The third step is to filter the system obtained in the second step to obtain a filtrate, and then cool the filtrate to a predetermined temperature for crystallization, and the crystallization temperature is -30~30°C;

[0029] In the fourth step, the system obtained in the third step is filtered, washed, and dried to obtain t...

Embodiment 2

[0030] Embodiment two: a kind of purification method of levetiracetam crude product

[0031] (A) Synthesis of crude levetiracetam

[0032] 84 g of anhydrous sodium sulfate were added to a suspension of 69.25 g (0.5 mol) (S)-2-aminobutanamide hydrochloride in 600 ml of dichloromethane at room temperature. The mixture was cooled to 0°C and 115 g of powdered potassium hydroxide were added, followed by 8.1 g (0.025 mol) of tetrabutylammonium bromide dissolved in 100 ml of methylene chloride. A solution obtained by dissolving 77.5g of 4-chlorobutyryl chloride in 100ml of dichloromethane was added dropwise at 0°C under vigorous stirring. After reacting for 5 hours, 29 g of powdered potassium hydroxide was added. Two hours later, filter the reaction system with diatomaceous earth, evaporate the filtrate under reduced pressure, add 100ml toluene to the residue, heat and reflux for 30 minutes, filter, evaporate the filtrate under reduced pressure to obtain 80g of levetiracetam crude ...

Embodiment 3

[0035] Embodiment three: a kind of purification method of levetiracetam crude product

[0036] Into the reaction flask, add 100g of acetone, 5g of purified water, add 20g of the crude levetiracetam obtained in Example 2, heat to 50°C and stir for 30 minutes, filter, and cool the filtrate to -5°C for crystallization for 5 hours, filter , washed with a small amount of cold acetone, and vacuum-dried at 40°C to obtain 15.3 g of the finished product. The yield of levetiracetam was 76.5%. The purity of the finished product measured by liquid chromatography was 99.98%, and the chirality was 99.95%.

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 relates to a method for purifying a levetiracetam crude product. The method is characterized by sequentially comprising the following steps of adding the levetiracetam crude product into a crystallizing system, wherein the weight ratio of the crystallizing system to the levetiracetam crude product is (1-10): 1, the crystallizing system is a mixed system of C3 to C6 ketone and purified water, and the weight ratio of the C3 to C6 ketone to the purified water is (10-50): 1; heating, and dissolving at 50 to 90 DEG C; filtering to obtain the filter liquid, cooling the filter liquid to a predetermined temperature to be crystallized, wherein the crystallization temperature is minus 30 to 30 DEG C; and finally filtering, washing and drying to obtain a levetiracetam finished product. By adopting the purification method, the purity of the levetiracetam finished product is more than or equal to 99.8 percent, and the chirality is more than or equal to 99.8 percent; the yield is high, and the method is simple to operate and applicable to the industrialized mass application.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a method for purifying crude levetiracetam. Background technique [0002] Levetiracetam (levetiracetam), the chemical name is (S)-α-ethyl-2-oxo-1-pyrrolidineacetamide, and its structural formula is shown in formula (I), [0003] [0004] It is a second-generation acetylcholine agonist developed by UCB Company in Belgium for the treatment of localized and secondary generalized epilepsy. It was approved by the US FDA in April 2000. [0005] At present, a large number of literatures have reported the synthesis method of levetiracetam, but there are relatively few materials related to purification. The original patent EP0162036 introduced two purification methods: (1) silica gel column (mobile phase: ethyl acetate : Methanol: Concentrated ammonia water = 85:12:3) for column purification, remove the solvent after passing through the column, and then recryst...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D207/27
CPCC07D207/27
Inventor 沈巍巍葛莹张薇徐敏
Owner SUZHOU TIANMA SPECIALTY CHEM
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com