Preparation method of Esomeprazole and preparation method of Esomeprazole sodium

A technology of esomeprazole sodium and esomeprazole, which is applied in the field of medicine, can solve the problems of cumbersome preparation process, achieve good stereoselectivity and avoid the effect of generation

Active Publication Date: 2014-08-06
SHOUGUANG FUKANG PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] At present, the preparation of esomeprazole sodium is mainly to prepare esomeprazole first, and then use sodium source to react with esomeprazole to generate sodium salt, and the preparation process is cumbersome

Method used

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  • Preparation method of Esomeprazole and preparation method of Esomeprazole sodium
  • Preparation method of Esomeprazole and preparation method of Esomeprazole sodium
  • Preparation method of Esomeprazole and preparation method of Esomeprazole sodium

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preparation example Construction

[0043] The invention provides a kind of preparation method of esomeprazole, comprising:

[0044]5-methoxy-2-(((4-methoxy-3,5-dimethyl-2-pyridyl)methyl)thio)-1H-benzimidazole, (1S,2S)- (-)-1,2-cyclohexanediamine-D-tartrate, cobalt naphthenate and water are added to an organic solvent for reaction to obtain a reaction solution;

[0045] Oxidant and water are added into the reaction liquid, and esomeprazole is obtained after reaction.

[0046] The present invention first adds 5-methoxy-2-(((4-methoxy-3,5-dimethyl-2-pyridyl)methyl)thio)-1H-benzimidazole into the organic solvent , and heat up to dissolve it to obtain a clear solution; the organic solvent is preferably ethyl acetate, toluene or acetone, more preferably ethyl acetate; the dissolution temperature can be 60°C to 75°C, preferably 62°C to 68°C ℃.

[0047] Cool the clear solution, add (1S,2S)-(-)-1,2-cyclohexanediamine-D-tartrate, cobalt naphthenate and water, and stir to obtain a reaction solution; the (1S, 2S)-(-)-1...

Embodiment 1

[0079] 15 g (45 mmol) of 5-methoxy-2-(((4-methoxy-3,5-dimethyl-2-pyridyl)methyl)thio)-1H-benzimidazole Add 75ml of ethyl acetate, heat up to 65°C, after dissolving, lower the temperature to 55°C, add 11.89g (45mmol) (1S,2S)-(-)-1,2-cyclohexanediamine- D-tartrate and 14.09 g (45 mmol) cobalt naphthenate, add a small amount of purified water at the same time, stir for 2 hours, lower the temperature to 0-5 ° C, add 2 ml of water at this temperature, and use 2-3 hours to dissolve 3.55 g (45 mmol) of sodium peroxide was slowly added to the reaction solution. After the addition was complete, the reaction was carried out at 0-5° C. for 2 hours, and the end point of the reaction was determined by TLC. After the reaction was completed, the solid was obtained by filtration, washed with petroleum ether, and dried to obtain 13.4 g of esomeprazole sodium, with a yield of 80%.

[0080] Through content determination of the esomeprazole sodium, the content is ≥ 98.0%, and the single compound...

Embodiment 2

[0100] 15 g (45 mmol) of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfanyl]-1H-benzimidazole Add 75ml of ethyl acetate, heat up to 65°C, after dissolving, lower the temperature to 55°C, add 5.28g (20mmol) (1S,2S)-(-)-1,2-cyclohexanediamine- D-tartrate and 6.26 g (20 mmol) cobalt naphthenate, add a small amount of purified water at the same time, stir for 2 hours, lower the temperature to 0-5 ° C, add 2 ml of water at this temperature, and use 2-3 hours to dissolve 3.55 g (45 mmol) of sodium peroxide was slowly added to the reaction solution. After the addition was complete, the reaction was carried out at 0-5° C. for 2 hours, and the end point of the reaction was determined by TLC. After the reaction was completed, the solid was obtained by filtration, washed with petroleum ether, and dried to obtain 13.4 g of esomeprazole sodium, with a yield of 80%.

[0101] Through content determination of the esomeprazole sodium, the content is ≥ 98.0%, and the single compou...

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Abstract

The invention provides a preparation method of Esomeprazole and a preparation method of Esomeprazole sodium, and (1S,2S)-(-)-1,2- hexamethylene diamine-D-tartrate is used as a chiral ligand, cobaltous naphthenate is used as catalyst, and Esomeprazole is prepared by asymmetric oxidation of 2-(((4-methoxy-3,5-dimethyl-2-pyridyl)methyl)sulfur-base)-1H-benzimidazole under the effect of catalyst with catalysis amount, and the prepared Esomeprazole has a better stereoselectivity and generation of peroxide sulfone is avoided. Simultaneously, sodium hypochlorite or sodium peroxide are used as oxidizing agent for preparing Esomeprazole sodium, and the sodium containing compound in the reaction process is used as oxidizing agent and sodium source, thereby the oxidation reaction and the salt forming reaction can be completed in the same reaction system with simple synthesis process.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a preparation method of esomeprazole and a preparation method of esomeprazole sodium. Background technique [0002] Esomeprazole is the S-isomer of omeprazole, and its chemical name is: 5-methoxy-2-((S)-((4-methoxy-3,5-dimethyl -2-pyridyl)methyl)sulfinyl)-1H-benzimidazole, the molecular formula is: C 17 h 19 N 3 o 3 S. The preparation methods of esomeprazole include: racemic body omeprazole resolution method, omeprazole sulfide asymmetric catalytic oxidation method and biochemical oxidation method, but because racemic body omeprazole The resolution method will waste half of the omeprazole, causing environmental pollution and economic loss, and the price of the optically active resolving agent is also relatively expensive, so the large-scale use of this resolution method in industry is limited; in addition, Due to the complicated operation and low selectivity of the biochem...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D401/12
Inventor 宋伟国张祥敏高东圣董良军杨磊夏艳田梅王伟刘东
Owner SHOUGUANG FUKANG PHARMA
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