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Method for preparing esomeprazole and salts thereof

A technology of esomeprazole and omeprazole sulfide, applied in the direction of organic chemistry and the like, can solve the problems of serious environmental pollution and high cost, and achieve the effects of high stereoselectivity, low production cost and stable process

Inactive Publication Date: 2012-01-25
刘强
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] The technical problem to be solved in the present invention is to overcome the disadvantages of relatively serious environmental pollution and high cost in the prior art, and provide a kind of esomeprazole and esomeprazole with higher yield, environmental friendliness, lower cost and stable process. The preparation method of its salt

Method used

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  • Method for preparing esomeprazole and salts thereof
  • Method for preparing esomeprazole and salts thereof
  • Method for preparing esomeprazole and salts thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Dissolve 5g of omeprazole sulfide in 50mL of isopropanol, add 1.54g of triethylamine, stir and react for 30 minutes at room temperature, then add 1.74g of (1R)-(- )-camphorsulfonazine, stirring and reacting for 20 hours, TLC (developing solvent: acetone: petroleum ether=1: 2, color development: ultraviolet) detected that the reaction was complete. Suction filtration, wash the filter cake with isopropanol, add about 60mL of water after the filtrate is concentrated, adjust its pH to 7-9 with hydrochloric acid solution, extract 3 times with ethyl acetate, take the organic phase, concentrate and dry to obtain foamy solid Esso Meprazole 3.96g, yield: 75.5%. HPLC assay ee: 99.27%.

Embodiment 2

[0047] Dissolve 5g of omeprazole sulfide in 80mL of toluene, add 4.62g of DBU, stir and react for 60 minutes at room temperature, then add 3.48g of (1R)-(-)-methyl Camphorsulfonazine was stirred and reacted for 6 hours, and the reaction was detected to be complete by TLC (developer: acetone:petroleum ether=1:2, color development: ultraviolet). Filtrate with suction, wash the filter cake with toluene, add about 40mL of water after the filtrate is concentrated, adjust its pH to 7-9 with acetic acid solution, extract 4 times with dichloromethane, take the organic phase, concentrate, and dry to obtain esomemera as a foamy solid Azole 4.08g, yield: 77.8%. HPLC assay ee: 99.24%.

Embodiment 3

[0049] Dissolve 5g of omeprazole sulfide in 100mL of ethanol, add 3.04g of sodium hydroxide, stir and react for 90 minutes at room temperature, then add 6.96g of (1R)-(-)-camphorsulfonate at 75°C to 80°C Dumbazine was stirred and reacted for 2 hours, and the reaction was detected to be complete by TLC (developer: acetone:petroleum ether=1:2, color development: ultraviolet). Suction filtration, wash the filter cake with ethanol, add about 80mL water after the filtrate is concentrated, adjust its pH to 7-9 with propionic acid solution, extract 3 times with ethyl acetate:toluene (1:1), take the organic phase to concentrate, dry, 4.16 g of foamy solid esomeprazole was obtained, yield: 79.3%. HPLC assay ee: 99.36%.

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Abstract

The invention relates to a novel method for preparing esomeprazole and sodium salts, magnesium salts, lithium salts, potassium salts, calcium salts and ammonium salts thereof. The esomeprazole is prepared by oxidizing omeprazole sulfide; and an oxidant is a chiral camphorsulfonyloxaziridine compound. The method comprises the following steps of: dissolving the omeprazole sulfide into a solvent, adding an alkaline reagent, stirring for 30 to 90 minutes at room temperature, adjusting the temperature to -30 to 200 DEG C, adding the oxidant, namely the chiral camphorsulfonyloxaziridine compound, and stirring and reacting for 0.5 to 20 hours to obtain the esomeprazole. In the method, a chiral ligand and a metal compound are not required to be added, the introduction of heavy metals is avoided in the reaction, and the chiral camphorsulfonyloxaziridine compound which participates in the oxidation reaction can be recycled, so that the utilization rate of the oxidant is remarkably improved and the production cost is remarkably reduced; and the prepared esomeprazole in high in purity and yield.

Description

technical field [0001] The invention relates to a new method for preparing esomeprazole and its sodium salt, magnesium salt, lithium salt, potassium salt, calcium salt and ammonium salt. Background technique [0002] Omeprazole is the first proton pump inhibitor (PPI) on the market. It is mainly metabolized by the isoenzyme systems CYF2C19 and CYP3A4 of cytochrome P450, and there is a polymorphism in the CYF2C19 gene, which has two phenotypes : rapid metabolism (EM) type and slow metabolism (PM) type, wherein 12%-22% of Asians belong to PM type. (R)-omeprazole is mainly metabolized into inactive substances by CYP2C19, while (S)-omeprazole is more metabolized by CYP3A4, and the metabolic rate is very slow. Therefore, omeprazole in PM population The maximum blood concentration is about 7 times higher than that of EM patients, and this difference will lead to huge differences in the efficacy of different patients. [0003] Omeprazole is a 1:1 mixture of R-type and S-type opti...

Claims

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Application Information

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IPC IPC(8): C07D401/12
Inventor 刘强
Owner 刘强
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