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Preparation method for esomeprazole

A technology of esomeprazole and azole, which is applied in the field of drug synthesis, can solve the problems of heavy metal pollution, environmental harm, single chirality and the like, and achieves the effects of simple operation, low cost and easy availability of raw materials

Active Publication Date: 2014-10-15
NEW FOUNDER HLDG DEV LLC +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method is a more commonly used technology at this stage. Its principle is to use chiral ligands to complex with metals to carry out asymmetric catalytic oxidation of thioethers to obtain esomeprazole products with single chirality. This method has heavy metal pollution. , harmful to the environment

Method used

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  • Preparation method for esomeprazole
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  • Preparation method for esomeprazole

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preparation example Construction

[0092] C. the preparation method of esomeprazole

[0093] The present invention also provides a method for preparing esomeprazole, wherein said esomeprazole is shown in formula VII:

[0094]

[0095] The methods described include:

[0096] The following Grignard reaction occurs between the chiral compound shown in formula VI and the Grignard reagent shown in formula III, thereby obtaining the described esomeprazole:

[0097]

[0098] Wherein, M is magnesium or zinc, preferably magnesium; X is halogen, preferably chlorine, bromine or iodine, more preferably chlorine.

[0099] Preferably, the molar ratio of intermediate VI to intermediate III Grignard reagent of the Grignard reaction is 1:(1-1.2); more preferably 1:(1-1.1). Too high or too low a molar ratio will lead to excess raw materials.

[0100]Preferably, the Grignard reaction is carried out in an aprotic solvent, and the aprotic solvent is preferably tetrahydrofuran, methyl tert-butyl ether, toluene or xylene, pr...

Embodiment 1

[0149] Embodiment 1: the preparation of the Grignard reagent shown in formula III:

[0150] Keep warm at about 20°C, replace the reaction system with nitrogen, add 150ml of tetrahydrofuran (hereinafter referred to as THF) and 68.0g (2.80mol) of magnesium chips (after pretreatment), and 12.7g (0.05mol) of iodine into a 1000ml reaction bottle, and stir for 1 Hours, the temperature was raised to 30°C, and at the same time, 464.3g (2.50mol) and 12.7g (0.05mol) of 2-(chloromethyl)-4-methoxyl-3,5-lutidine dissolved in 150ml THF were slowly added dropwise. ) iodine mixture, after dropping, keep warm at 30°C for 5 hours, cool to 20°C to 25°C, and set aside.

[0151] Among them, the pretreatment method of magnesium chips is as follows: stir and wash with 5% hydrochloric acid for 30 minutes, quickly filter and rinse with acetone (minimize the time of contact with air), and use it immediately after vacuum drying.

Embodiment 2

[0152] Embodiment 2: the preparation of the Grignard reagent shown in formula III:

[0153] Keep warm at about 20°C, replace the reaction system with nitrogen, add 150ml of tetrahydrofuran (hereinafter referred to as THF) and 183.1g (2.80mol) of zinc dust (after pretreatment), and 12.7g (0.05mol) of iodine into a 1000ml reaction bottle, and stir for 1 Hours, the temperature was raised to 30°C, and at the same time, 464.3g (2.50mol) and 12.7g (0.05mol) of 2-(chloromethyl)-4-methoxyl-3,5-lutidine dissolved in 150ml THF were slowly added dropwise. ) iodine mixture, after dropping, keep warm at 30°C for 8 hours, cool to 20°C to 25°C, and set aside.

[0154] Among them, the pretreatment method of zinc shavings is as follows: stir and wash with 5% hydrochloric acid for 30 minutes, quickly filter and rinse with acetone (minimize the time of contact with air), and use it immediately after vacuum drying.

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Abstract

The invention provides a preparation method for esomeprazole. The preparation method for esomeprazole comprises: enabling a chiral compound shown as a formula VI and a Grignard reagent shown as a formula III to perform a Grignard reaction shown in the specification, so as to obtain esomeprazole. In the reaction, M is magnesium or zinc, preferably is magnesium, and X is a halogen, preferably is chlorine, bromine or iodine, and more preferably is chlorine. The preparation method comprises the following advantages and active effects: esomeprazole prepared by employing the method is good in purity and high in yield, and the purity and the yield both reach about 90%; the whole preparation technological process does not relate to an asymmetric oxidation step, so that the preparation method does not cause heavy metal pollution; and also the preparation method is simple in operation, easily available in raw materials and low in cost, and is suitable for industrialized large-scale production.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular, relates to a new intermediate V for preparing esomeprazole or its sodium salt and a preparation method thereof, and an intermediate V for preparing esomeprazole or its sodium salt Intermediate VI and its preparation method, esomeprazole preparation method, and esomeprazole sodium preparation method. Background technique [0002] The chemical name of omeprazole is 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl]-1H-benzo Imidazole, developed by AstraZeneca in Sweden, was the first proton pump inhibitor to be marketed. [0003] Esomeprazole is the S-isomer of omeprazole, the 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, molecular weight: 345.42, CAS number: 119141-88-7. The chemical structural formula is shown in the following formula VII: [0004] [...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/12C07D235/28
CPCC07D213/68C07D235/28C07D401/12
Inventor 王威徐虹付彪
Owner NEW FOUNDER HLDG DEV LLC
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