Esomeprazole and preparation method of magnesium trihydrate of esomeprazole

A technology for esomeprazole and omeprazole sodium salt, which is applied in the field of drug synthesis, can solve the problems of low esomeprazole yield, low enantiomeric excess value, unsuitable for industrial production and the like, and achieves cost Low, short reaction time, easy refining effect

Inactive Publication Date: 2013-03-27
HUNAN FANGSHENG PHARMACEUTICAL CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] The object of the present invention is to provide a kind of preparation method of esomeprazole and magnesium salt trihydrate thereof, to solve the low yield of esomeprazole in the prior art, the enantiomeric excess value of resolution process is lower , low purity, not suitable for technical problems related to industrial production

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  • Esomeprazole and preparation method of magnesium trihydrate of esomeprazole

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preparation example Construction

[0038] One aspect of the present invention provides a kind of preparation method of esomeprazole, comprises the following steps:

[0039] (1) Carrying out acid-base neutralization reaction of racemic omeprazole and inorganic base in alcohol solution to obtain omeprazole sodium salt;

[0040] (2) Dissolving omeprazole sodium salt, organometallic complexing agent, chelating agent, and organic base in an organic solvent for complexation reaction to obtain esomeprazole complex;

[0041] (3) Condensing the esomeprazole complex with S-mandelic acid to obtain the esomeprazole mandelate complex;

[0042] (4) dissolving the esomeprazole mandelate complex in an acetone solution and filtering to obtain the S-omeprazole-S-mandelate complex;

[0043] (5) Suspending the S-omeprazole-S-mandelate complex in the first solvent to obtain a suspension, adjusting the pH of the suspension to 8~10 to obtain esomeprazole, the first solvent includes 30~32v / v% alkaline aqueous solution and 68~70v / v% ...

Embodiment 1

[0067] Preparation of esomeprazole:

[0068] (1) Weigh 5L of methanol and 8L of isopropanol into a 20L reactor, weigh 348.0g of sodium hydroxide and put it into the reactor, adjust the temperature in the reactor to 20°C, and stir mechanically for 0.5h to obtain solution 1. Suction filter the solution with diatomaceous earth to obtain the filtrate, take 10 L of the filtrate into the reaction kettle, add 2 kg of racemic omeprazole, stir mechanically for 2 hours, and spin dry under reduced pressure at 45°C to obtain a white solid. Add 4L of ethyl acetate to the reaction kettle containing the obtained white solid, stir for 1 hour, filter with suction, wash the filter cake with 1.6L of ethyl acetate, and dry the filter cake at 40°C for 8 hours to obtain 2.2kg with a water content of 1.5%. omeprazole sodium white solid, 2.2kg of omeprazole sodium is ground into powder, added to 2.5L cyclohexane and 193ml deionized water, and the mixed solution formed continues to stir for 2h and the...

Embodiment 2

[0078] Preparation of esomeprazole:

[0079](1) Weigh 5L of methanol and 8L of isopropanol into a 20L reactor, weigh 348.0g of sodium hydroxide and put it into the reactor, adjust the temperature of the reactor to 25°C, and stir mechanically for 0.5h to obtain solution 1. Suction filter the solution with diatomaceous earth to obtain the filtrate, take 10 L of the filtrate into the reaction kettle, add 2 kg of racemic omeprazole, stir mechanically for 2 hours, and spin dry under reduced pressure at 45°C to obtain a white solid. Add 4L of ethyl acetate to the reaction kettle containing the obtained white solid and stir for 1h, filter with suction, wash the filter cake with 1.6L of ethyl acetate, and dry the filter cake at 40°C for 8h to obtain 2.2kg of omeprazole Sodium white solid, 2.2kg of omeprazole sodium is ground into powder, added to 2.5L of cyclohexane and 193ml of deionized water, and the resulting mixed solution is continuously stirred for 2 hours, then suction filtere...

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Abstract

The invention provides esomeprazole and a preparation method of magnesium trihydrate of the esomeprazole. The preparation method includes the following steps of subjecting racemization omeprazole and inorganic base to acid-base neutralization reaction in an alcoholic solution to obtain racemization omeprazole sodium salt; dissolving omeprazole sodium salt, organic metal coordination agents, chelating agents and organic base in an organic solvent for complex reaction to obtain esomeprazole complex; subjecting S-mandelic acid and the esomeprazole complex to condensation reaction to obtain an esomeprazole mandelate compound; dissolving the esomeprazole mandelate compound in an acetone solution, and performing filtering to obtain S-omeprazole-S-mandelate compound; and suspending the S-omeprazole-S-mandelate compound in a first solvent to obtain a suspension solution, and adjusting potential of hydrogen (pH) of the suspension solution to be 8-10 to obtain the esomeprazole, wherein the first solvent includes 30-32v / v% of an alkaline aqueous solution and 68-70v / v% of an organic solvent. By means of the preparation method, the technical problem that the yield and the purity of the esomeprazole in prior art are low is solved.

Description

technical field [0001] The present invention relates to the field of drug synthesis, in particular, to a preparation method of esomeprazole, and another aspect of the present invention also provides a preparation method of esomeprazole magnesium salt trihydrate. Background technique [0002] Omeprazole (Omeprazole) is developed by Astra Company in Sweden. It is the world's first clinical proton pump inhibitor for the treatment of gastric ulcer, duodenal ulcer and reflux esophagitis. [0003] The chemical structure of omeprazole consists of three parts, the benzoimidazole ring and the pyridine ring are connected through the methyl sulfoxide group. It is optically active due to the chirality of the sulfur atom on the sulfoxide group. Esomeprazole is the S-isomer of omeprazole, and its R-configuration isomer mainly contains CYP 2 C 19 Metabolism, the rate of metabolism to inactive substances is fast; and the S-isomer has more CYP 3 A 4 metabolism, CYP 2 C 19 The dependen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/12
Inventor 张庆华孙先仁
Owner HUNAN FANGSHENG PHARMACEUTICAL CO LTD
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