Method for preparing Levetiracetam

A compound and basic reagent technology, applied in the field of drug preparation, can solve problems such as unsatisfactory optical purity of reaction products, low total product yield, complicated reaction steps, etc., and achieve the required conditions for the reaction and the reaction process is simple and inexpensive Low cost and high total yield

Inactive Publication Date: 2009-10-07
WUXI SUNFU PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The raw materials and solvents required for the synthesis method of levetiracetam disclosed in the above prior art are expensive, the reaction steps are complicated, and the optical purity of the reaction product is not ideal, and the total yield of the resulting product is not high.

Method used

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  • Method for preparing Levetiracetam
  • Method for preparing Levetiracetam
  • Method for preparing Levetiracetam

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] (1) Compound (II) is the synthesis of (S)-2-amino-4-hydroxybutyric acid:

[0036] Dissolve 7.5g of L-methionine (0.05mol) in 200ml of water, add 10ml (0.16mol) of methyl iodide dropwise, seal and stir at 30°C for 24 hours, concentrate under reduced pressure to 100ml to remove excess methyl iodide, add 5.00g of KHCO 3 (0.05mol) heated to reflux for 10h, vacuum-dried at 60°C, added 100ml of methanol and 1ml of water to dissolve, added dropwise concentrated hydrochloric acid to adjust the pH value to 5-6, filtered while hot, concentrated to 30ml, frozen and crystallized, suction filtered, 70 After drying at °C for 5 hours, 4.55 g of white crystals of (S)-2-amino-4-hydroxybutyric acid were obtained, with a yield of 70%.

[0037] (2) Compound (III) is the synthesis of (S)-2-(4-chlorobutyrylamide)-4-hydroxybutyric acid:

[0038] Take 3.23g (0.027mol) of (S)-2-amino-4-hydroxybutyric acid synthesized in step (1), add 9.07g (0.108mol) of sodium bicarbonate and mix well, add to ...

Embodiment 2

[0044] (1) Compound (II) is the synthesis of (S)-2-amino-4-hydroxybutyric acid:

[0045] Dissolve 7.5g of L-methionine (0.05mol) in 200ml of water, add 8ml (0.13mol) of methyl iodide dropwise, seal and stir at 30°C for 24 hours, concentrate under reduced pressure to 100ml to remove excess methyl iodide, and add 2.00g of sodium hydroxide (0.05mol) heated to reflux for 5h, vacuum-dried at 50°C, added 100ml of ethanol and 1ml of water to dissolve, added dropwise concentrated hydrochloric acid to adjust the pH value to 5-6, filtered while hot, concentrated to 30ml, frozen and crystallized, suction filtered, 70 After drying at °C for 5 hours, 5.00 g of white crystals of (S)-2-amino-4-hydroxybutyric acid were obtained, with a yield of 76.9%.

[0046] (2) Compound (III) is the synthesis of (S)-2-(4-chlorobutyrylamide)-4-hydroxybutyric acid:

[0047] Take 3.23g (0.027mol) of (S)-2-amino-4-hydroxybutyric acid synthesized in step (1), add 11.45g (0.108mol) of sodium carbonate and mix w...

Embodiment 3

[0053] (1) Compound (II) is the synthesis of (S)-2-amino-4-hydroxybutyric acid:

[0054] Dissolve 7.5g of L-methionine (0.05mol) in 200ml of water, add 12.5ml (0.20mol) of methyl iodide dropwise, seal and stir at 30°C for 24 hours, concentrate under reduced pressure to 100ml to remove excess methyl iodide, add 5.30g of sodium carbonate (0.05mol) heated to reflux for 11h, vacuum-dried at 50°C, added 100ml of acetone and 1ml of water to dissolve, added dropwise concentrated hydrochloric acid to adjust the pH value to 5-6, filtered while hot, concentrated to 30ml, frozen and crystallized, suction filtered, 60 After drying at °C for 5 hours, 4.12 g of white crystals of (S)-2-amino-4-hydroxybutyric acid were obtained, with a yield of 63%.

[0055] (2) Compound (III) is the synthesis of (S)-2-(4-chlorobutyrylamide)-4-hydroxybutyric acid:

[0056] Take 3.23g (0.027mol) of (S)-2-amino-4-hydroxybutyric acid synthesized in step (1), add 2.16g (0.054mol) of sodium hydroxide and mix well...

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Abstract

The invention discloses a method for preparing Levetiracetam. In the method, L-methionine is used as a raw material to prepare the Levetiracetam through the steps including hydroxylation of methylthio, acidylation of amido, amidation of carboxylic acid as well as cyclization. The raw material used by the method for preparing Levetiracetam is natural amino acid-L-methionine which has broad sources and low cost. Moreover, the method for preparing Levetiracetam has high total yield coefficient; the optical purity of the obtained product is high; the conditions needed for the reaction and the reaction process are simple; and an internal compensation product obtained by a complex splitting method is avoided, and a new choice is provided for preparing and producing the Levetiracetam.

Description

technical field [0001] The invention relates to a method for preparing medicine, in particular to a method for preparing levetiracetam. Background technique [0002] Levetiracetam (levetiracetam) is a second-generation acetylcholine agonist developed by UCB Company in Belgium. It is a derivative of pyrrolidone and is used for the treatment of localized and secondary generalized epilepsy. The drug was approved by the US FDA in April 2000. Because the drug has selective protective localization and pharmacological effects of primary generalized epilepsy, it is a new type of broad-spectrum antiepileptic drug with good tolerance and low drug interaction, and has broad clinical application prospects. [0003] The chemical name of levetiracetam is: (S)-α-ethyl-2-oxo-1-acetamide pyrrolidine, and its English name is: (S)-2-(2-Oxopyrrolidin-1-yl) butanamide, molecular formula: C 8 h 14 N 2 o 2 , the molecular weight is: 170.21, and its chemical structural formula is: [0004] ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D207/27
Inventor 沈立新卞禹卜刘福双吴鹏程姜坤
Owner WUXI SUNFU PHARMA
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