Industrialization production technology for tenofovir disoproxil fumarate

A production process and reaction technology, which is applied in the field of tenofovir preparation process, can solve the problems of harsh production conditions, high cost, and low yield of large-scale preparation, and achieve the effects of cost reduction, high yield, and high product purity

Inactive Publication Date: 2016-08-17
JINGMEN SHUAIBANG CHEM SCI & TECHCO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are many existing methods for preparing tenofovir, but there are still some technica...

Method used

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  • Industrialization production technology for tenofovir disoproxil fumarate
  • Industrialization production technology for tenofovir disoproxil fumarate
  • Industrialization production technology for tenofovir disoproxil fumarate

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preparation example Construction

[0018] (1) Preparation of R-propylene carbonate, add (R-1,2-propylene glycol), diethyl carbonate and sodium ethoxide to a glass-lined reactor, heat to 105-110°C, react for 7-9 hours, and react After termination, the unreacted diethyl carbonate is distilled off under reduced pressure, cooled to room temperature, insoluble matter is filtered off, and the filtrate is evaporated to remove the solvent to obtain the product R-propylene carbonate.

[0019] The chemical formula of the above synthesis reaction is:

[0020]

[0021] (2) Preparation of diethyl p-toluenesulfonyloxymethylphosphonate

[0022] Add absolute ethanol and diethyl phosphite to the glass-lined reaction kettle, stir, and the stirring is complete, open the lid of the kettle, put in paraformaldehyde and triethylamine, heat to 35-45°C and react for 0.5-1 hour, at 50- Incubate the reaction at 65°C for 4-6 hours, cool slightly to 30-40°C, filter the solid with diatomaceous earth, and rinse with a small amount of ethanol, comb...

specific Embodiment

[0029] The specific embodiment of the present invention is carried out according to the following steps:

[0030] (1) Preparation of R-propylene carbonate, add R-1,2-propylene glycol (38.05kg, 500mol), diethyl carbonate (70.88kg, 600 mol) and (3.4kg, 50mol) into the glass-lined reactor Sodium ethoxide, heated to 105-110°C, reacted for 8 hours, the reaction was terminated, the unreacted diethyl carbonate was distilled off under reduced pressure, cooled to room temperature, the insoluble matter was filtered off, the filtrate was evaporated to remove the solvent to obtain the product R-carbonic acid The propylene ester is 34.24kg, the purity is ≥99%, and the yield is 90%.

[0031] The chemical formula of the above synthesis reaction is:

[0032]

[0033] (2) Preparation of diethyl p-toluenesulfonyloxymethylphosphonate

[0034] Add absolute ethanol (51 kg, 1107 mol) and diethyl phosphite (22 kg, 159.3 mol) into the glass-lined reactor, stir, and after the stirring is complete, open the l...

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Abstract

An industrial production process of tenofovir, the production process steps are as follows: add R-1,2-propylene glycol, diethyl carbonate and sodium ethylate into the reaction kettle; add absolute ethanol and diphosphite Ethyl ester, stirring, after the stirring is completed, put in paraformaldehyde and triethylamine, after the reaction is complete, add anhydrous sodium sulfate, dry, filter, and distill out, the distilled product is diethyl p-toluenesulfonyloxymethylphosphonate Fine product; add adenine, R-propylene carbonate, DMF and NaOH in the reaction kettle, after the reaction is complete, add magnesium tert-butoxide, drop diethyl p-toluenesulfonyl phosphate, after the reaction is complete, add acetic acid, Concentrate under reduced pressure, add hydrochloric acid, filter, filter out the solid and dry under normal pressure to obtain PMPA fine product. The method has the advantages of high yield, high product purity and low impurity content, and can be fully industrialized.

Description

Technical field [0001] The invention relates to the field of preparation technology of tenofovir, in particular to an industrialized production process of tenofovir. Background technique [0002] Tenofovir (Compound I), also known as tenofovir, full Chinese name: (R)-9-(2-phosphate methoxypropyl)-adenine, is an AIDS antiviral drug, Tenofo Weiwei is also a key intermediate of tenofovir disoproxil fumarate (II), a more effective AIDS antiviral drug. Due to the good anti-AIDS activity of tenofovir, especially tenofovir disoproxil fumarate, it is widely used clinically. There are many existing methods for preparing tenofovir, but there are still some technical defects, such as high cost, low yield of large-scale preparation, and harsh manufacturing conditions. These all need to be further researched and improved. Therefore, it is necessary to develop a method of Tenofovir with high yield, low cost, easy preparation and suitable for industrial production. Summary of the invention ...

Claims

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Application Information

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IPC IPC(8): C07F9/6561
CPCC07F9/65616
Inventor 廖劲松
Owner JINGMEN SHUAIBANG CHEM SCI & TECHCO
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