Preparation process of the sodium salt of esomeprazole

A technology of esomeprazole and sodium alkoxide, which is applied in the field of esomeprazole sodium, can solve the problems of unsuitable industrial scale preparation, difficult stirring, and difficult removal of residual solvent due to the degradation of crude substances.

Inactive Publication Date: 2012-11-07
ESTEVE QUIMICA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, these methods involve complete distillation of the reaction solvent and are not suitable for industrial-scale preparations because they involve handling with small volu...

Method used

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  • Preparation process of the sodium salt of esomeprazole
  • Preparation process of the sodium salt of esomeprazole
  • Preparation process of the sodium salt of esomeprazole

Examples

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Embodiment 1

[0065] Embodiment 1: use the methanol solution of methyl isobutyl ketone and sodium methylate as solvent to prepare esomeprazole sodium

[0066] 30% sodium methoxide in methanol (4.7 mL, 25.3 mmol) was added dropwise to a solution of esomeprazole (8.5 g, 24.6 mmol; 2.2% sulfone) in methyl isobutyl ketone (60 mL) at room temperature. solution. The resulting slurry was stirred overnight. The solid was collected by filtration, washed with methyl isobutyl ketone (2×10 mL) acetone, and dried under reduced pressure at 50° C. to obtain esomeprazole sodium. Yield: 6.3 g (70%). Sulfone content: 0.33%.

Embodiment 2

[0067] Example 2: Preparation of Emmy using methyl isobutyl ketone / acetone and methanolic sodium methoxide Larazole Sodium

[0068] 30% sodium methoxide in methanol (4.7 mL, 25.3 mmol) was added dropwise to esomeprazole (8.5 g, 24.6 mmol; 2.2% sulfone, 4.7% R-enantiomer) in methylisobutyl solution in ketone (60 mL). The mixture was stirred for 15 minutes. Acetone (60 mL) was added over 30 minutes. The resulting slurry was stirred overnight at room temperature. The solid was collected by filtration, washed with acetone (2 x 10 mL), and dried under reduced pressure at 50 °C to afford esomeprazole sodium. Yield: 5.5 g (61%). Sulfone content: 0.17%. R-enantiomer content: 0.00%.

Embodiment 3

[0069] Example 3: Preparation of Emmy using methyl isobutyl ketone / acetone and methanolic sodium methoxide Larazole Sodium

[0070] 30% sodium methoxide in methanol (6.0 mL, 32.3 mmol) was added dropwise to esomeprazole (10.7 g, 31.0 mmol; 1.1% sulfone, 2.5% R-enantiomer) in methylisobutyl solution in ketone (75 mL). The mixture was stirred for 20 minutes. Acetone (75 mL) was added over 30 minutes. The resulting slurry was stirred overnight at room temperature. The solid was collected by filtration, washed with acetone (2 x 12.5 mL), and dried under reduced pressure at 50 °C to give esomeprazole sodium. Yield: 6.8 g (60%). Sulfone content: 0.06%. R-enantiomer content: 0.00%.

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Abstract

Preparation process of the sodium salt of a 2-(2-pyridylmethylsulfinyl)- benzimidazole derivative compound It comprises a preparation process of esomeprazole sodium substantially free of sulfone impurity comprising the steps of: a) combining either esomeprazole with a (C3-C8)-ketone or a mixture thereof, a sodium alkoxide, and a (C1-C5)-alcohol, or esomeprazole sodium with a (C3-C8)-ketone or a mixture thereof and a (C1-C5)-alcohol; and b) recovering the esomeprazole sodium formed from the reaction media by filtration.

Description

[0001] This application claims the benefit of European Patent Application No. 10382032 filed on 2010.02.12 and US Provisional Patent Application Serial No. 61313874 filed on 2010.03.15. field of invention [0002] The present invention relates to a method for preparing substantially free of sulfone impurity (5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl- 2-pyridyl)methyl]sulfonyl]-1H-benzimidazole esomeprazole sodium method. Background technique [0003] Esomeprazole is the compound 5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-1H- International Nonproprietary Name (INN) for benzimidazole. The CAS number of esomeprazole is 119141-88-7, and the CAS number of its sodium salt is 161796-78-7. The chemical structure of esomeprazole sodium is as follows: [0004] [0005] Esomeprazole and its base salts are proton pump inhibitors developed by AstraZeneca. They are potent inhibitors of gastric acid secretion and are therefore useful in the prevention and t...

Claims

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Application Information

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IPC IPC(8): C07D401/12A61K31/4439
CPCC07D401/12A61P1/04A61K31/4439
Inventor M·巴拉特拉圣马拉蒂R·贝伦古埃马埃默J·G·索尔索纳罗卡贝尔特
Owner ESTEVE QUIMICA
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