A kind of synthetic technique of levetiracetam

A technology of synthesis process and synthesis route, applied in the direction of organic chemistry, can solve the problems of high optical isomers, large safety hazards and cost investment, and achieve the effect of high product quality, low safety investment cost, and mild conditions

Active Publication Date: 2021-06-01
HONGGUAN BIO PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, during the conversion from carboxylic acid to amide, highly toxic control products such as alkyl chloroformate are used
In commercial mass production, there are great potential safety hazards and cost investment in safety
Simultaneously, the levetiracetam finished product obtained by this process has higher optical isomers

Method used

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  • A kind of synthetic technique of levetiracetam
  • A kind of synthetic technique of levetiracetam
  • A kind of synthetic technique of levetiracetam

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] The first step: the synthesis of (S)-2-(4-chlorobutanamide) butanamide

[0033] In a 2L reaction flask, add 1000mL of acetonitrile, add (S)-2-(4-chlorobutanamide)butyric acid (100.0g, 481.6mmol) under stirring, stir to dissolve, add (Boc) 2 O (126.1g, 577.8mmol), control the temperature in the reaction system to 20-30°C, slowly add pyridine (26.7g, 337.6mmol) dropwise to the reaction system for 20 minutes, and stir for 30 minutes after the addition is complete; Add ammonium bicarbonate (45.7 g, 578.1 mmol), and stir at 20 to 30°C for 5 to 8 hours; TLC spotting detects that the reaction of the raw materials is complete (developing solvent: ethyl acetate: glacial acetic acid = 100:1), and filter Remove the insoluble matter in the system, and concentrate the filtrate to dryness under reduced pressure; add the concentrate to acetone, heat to 60-70°C to dissolve until all dissolved, cool to 10-20°C, stir and crystallize for 2-3 hours; filter, reduce Drying under pressure ga...

Embodiment 2

[0037] The first step: the synthesis of (S)-2-(4-chlorobutanamide) butanamide

[0038] In a 2L reaction flask, add 1000mL of acetonitrile, add (S)-2-(4-chlorobutanamide)butyric acid (100.0g, 481.6mmol) under stirring, stir to dissolve, add (Boc) 2 O (126.1g, 577.8mmol), control the temperature in the reaction system to 20-30°C, slowly add pyridine (26.7g, 337.6mmol) dropwise to the reaction system for 20 minutes, and stir for 30 minutes after the addition is complete; Add ammonium carbonate (37.0g, 385.3mmol), stir and react at 20-30°C for 5-8 hours; TLC spot plate detection of raw material reaction is complete (developing solvent: ethyl acetate: glacial acetic acid = 100:1), filter to remove For the insoluble matter in the system, the filtrate is concentrated to dryness under reduced pressure; the concentrate is added to acetone, heated to 60-70°C to dissolve until completely dissolved, cooled to 10-20°C, stirred and crystallized for 2-3 hours; filtered, reduced pressure Aft...

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Abstract

The invention relates to the technical field of medicine preparation, in particular to a preparation method of an antiepileptic drug. A kind of synthetic technique of levetiracetam designed by the present invention, take (S)-2-(4-chlorobutanamide) butanoic acid as starting raw material, take pyridine as base, (Boc) 2 O is the activating reagent of carboxylic acid, and ammonium salt is added to obtain (S)-2-(4-chlorobutanamide) butyramide, and finally the cyclization reaction is carried out in the presence of alkali to obtain levetiracetam. The process does not require chemical splitting, does not use highly toxic or corrosive chemical reagents, is simple to operate, has mild conditions, is environmentally friendly and has high-quality finished products, and is suitable for industrial production.

Description

technical field [0001] The invention relates to the technical field of medicine preparation, in particular to a preparation method of an antiepileptic drug. Background technique [0002] Epilepsy is a chronic syndrome of transient brain dysfunction, a common disease caused by neuronal synapse lesions. It is understood that there are tens of millions of epilepsy patients worldwide, a few of them can be completely treated, and most of them need to insist on long-term use of antiepileptic drugs to reduce seizures and create a good quality of life for patients. After a century of development, from the initial use of potassium bromide to the appearance of phenobarbital, and then to the advent of phenytoin and valproic acid in the last century, great progress has been made in the field of epilepsy treatment. Levetiracetam is a pyrrolidone antiepileptic drug, which can effectively control epileptic seizures. It has the characteristics of high therapeutic index, good safety, and mi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D207/27
CPCC07D207/27
Inventor 于学彬卢天翼朱金龙吴杰张超
Owner HONGGUAN BIO PHARMA CO LTD
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