Method for preparing oseltamivir phosphate by azide process

An oseltamivir phosphate and process technology, which is applied in the field of preparing oseltamivir phosphate by an azide process, can solve problems such as excessive heavy metals in diallylamine, and reduce the cost of environmental treatment of enterprises, with low cost and high yield. Effect

Pending Publication Date: 2020-10-09
YICHANG HEC CHANGJIANG PHARMA CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0013] The technical problem to be solved by the present invention is a method for preparing oseltamivir phosphate by an azide process, so as to overcome the problems of using expensive palladium acetate and highly corrosive diallylamine and excessive heavy metals in the prior art

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  • Method for preparing oseltamivir phosphate by azide process
  • Method for preparing oseltamivir phosphate by azide process
  • Method for preparing oseltamivir phosphate by azide process

Examples

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Embodiment 1

[0046] A method for preparing oseltamivir phosphate by an azide process, the synthetic route of said oseltamivir phosphate is as follows:

[0047]

[0048] Step (1): The intermediate (30.94g, 0.1mol) shown in formula (Ⅲ) was dissolved in 300mL N,N-dimethylformamide, and sodium azide (16.25g, 0.25mol) and ammonium chloride (16.05 g, 0.3mol). The system was heated to 70-75°C for 16 hours, and cooled to room temperature after the reaction was completed. Then the reaction system was poured into 1000mL water, extracted with ethyl acetate (200mL×3), the organic phases were combined, and concentrated on a rotary evaporator to obtain an oily crude product. The crude product was dissolved in 100 mL of methyl tert-butyl ether, stirred at -20°C for 20 h, a white solid was precipitated, and 28.4 g of the intermediate of formula (IV) was obtained by suction filtration, with a yield of 80.6%.

[0049] Step (2): Dissolve the intermediate of formula (IV) obtained in step (1) in 100 mL of...

Embodiment 3

[0056] The intermediate of formula (Ⅴ) was dissolved in 100 mL of ethanol, and 20 mL of water and about 10 drops of glacial acetic acid were added. Cool down to 0°C (±5°C) and add tributylphosphine (25.1g, 0.096mol) dissolved in 50mL of ethanol dropwise in about 1h, and rinse the dropping funnel with a small amount of ethanol. The reaction system continued to stir at this temperature for 90 minutes, then raised the temperature to about 25°C and stirred for 3 hours to release nitrogen. After the reaction was completed, it was concentrated to dryness under reduced pressure to obtain an oily crude intermediate of formula (VI).

[0057] The crude intermediate of formula (VI) was dissolved in 100 mL of trifluoroacetic acid, and the temperature was raised to 50° C. for 2 h. After the reaction was completed, it was concentrated on a rotary evaporator, and toluene was added to dry up excess trifluoroacetic acid. Add 100mL toluene and 100mL water to the concentrated solution, stir vi...

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Abstract

The invention belongs to the field of pharmaceutical chemicals, and particularly relates to a method for preparing oseltamivir phosphate by an azide process. The method comprises the following steps:reacting a compound shown in a formula (III) with sodium azide and ammonium chloride, opening a nitrogen heterocyclic ring, performing acetylation, reducing an azide group, removing tert-butyl, salifying with phosphoric acid, and purifying to obtain pure oseltamivir phosphate shown in a formula (I). According to the method, diallylamine with strong corrosivity and expensive palladium acetate do not need to be used so that the enterprise cost is reduced.

Description

technical field [0001] The invention relates to the field of medicine preparation, in particular to a method for preparing oseltamivir phosphate by an azide process. Background technique [0002] Oseltamivir phosphate is the most commonly used and one of the most effective drugs against avian influenza, influenza A H1N1 virus and influenza B virus, which can greatly reduce the occurrence of influenza complications. Its mechanism of action is through oral administration of oseltamivir phosphate, which is metabolized in the human body to produce a substance similar to viral neuraminidase, which competes in the process of virus reproduction and interferes with the release of the virus from infected cells, thereby reducing the spread of influenza virus . [0003] Oseltamivir phosphate structural formula (I): [0004] [0005] At present, there are many routes for synthesizing oseltamivir phosphate, which are divided into azide route and non-azide route. [0006] Among them...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C231/08C07C231/12C07C233/52C07C247/14
CPCC07C231/08C07C231/12C07C247/14C07C2601/16C07C233/52
Inventor 郭曼唐金龙李晓曦
Owner YICHANG HEC CHANGJIANG PHARMA CO LTD
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