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Preparation method of (R)-propene carbonate

A technology of propylene carbonate and propylene oxide, applied in the field of preparation of Novovir intermediates, can solve the problems of high production risk and high equipment requirements, and achieve the effects of low risk, less equipment investment and high yield

Inactive Publication Date: 2012-03-28
上海科利生物医药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, it needs to be synthesized under 30 atmospheres in production, which requires high equipment and high production risk.

Method used

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  • Preparation method of (R)-propene carbonate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] (1) Put 116 grams of (R)-propylene oxide and 1 gram of epoxyhydrolase ECU1040 into the reaction bottle, cool to 5°C in an ice-water bath, and add 50 grams of water dropwise. Control the temperature not to exceed 5°C. After dropping, the ice-water bath was removed, and the temperature was naturally raised to room temperature. The reaction was continued for 24 hours, and the reaction was stopped. Atmospheric pressure distilled (R)-propylene oxide 53 g, chemical purity 99.68%, optical purity 99.55% e.e. Yield 91.38%.

[0021] (2) Put 50g of (R)-propylene oxide and 200ml of ethanol obtained above into a 500mL reaction bottle, cool to 16°C, add 0.6g of cinchona base and 1.8g of triethylamine successively, stir for 15 minutes and then pass in carbon dioxide gas , keep the temperature not higher than 20°C. After 20 hours of reaction, carbon dioxide gas was no longer absorbed. The ethanol solvent was recovered by heating and atmospheric distillation, and 85.62 grams of pro...

Embodiment 2

[0023] (1) Put 116 grams of (R)-propylene oxide and 2.3 grams of epoxyhydrolase ECU1040 into the reaction bottle, cool to 0° C. in an ice-water bath, and add 22 grams of water dropwise. Control the temperature not to exceed 5°C. After dropping, the ice-water bath was removed, and the temperature was naturally raised to room temperature. The reaction was continued for 24 hours, and the reaction was stopped. Atmospheric pressure distilled 58 g of (R)-propylene oxide with a chemical purity of 99.73% and an optical purity of 99.65% e.e. Yield 92.38%.

[0024] (2) Put 50g of (R)-propylene oxide and 180ml of methanol obtained above into a 500mL reaction bottle, cool to 12°C, add 1.0g of cinchona base and 2.5g of ethylenediamine successively, stir for 15 minutes and then introduce carbon dioxide Gas, keep the temperature not higher than 20°C. After 24 hours of reaction, carbon dioxide gas was no longer absorbed. The methanol solvent was recovered under normal pressure by heating...

Embodiment 3

[0026] (1) Put 116 grams of (R)-propylene oxide and 1.1 grams of epoxyhydrolase ECU1040 into the reaction bottle, cool in an ice-water bath to 0-5°C, and add 232 grams of water dropwise. Control the temperature not to exceed 5°C. After dropping, the ice-water bath was removed, and the temperature was naturally raised to room temperature. The reaction was continued for 24 hours, and the reaction was stopped. 55 g of (R)-propylene oxide was distilled out under atmospheric pressure, with a chemical purity of 99.68% and an optical purity of 99.57% e.e. The yield is 91.68%.

[0027] (2) Put 50g of (R)-propylene oxide and 200ml of tert-butanol obtained above into a 500mL reaction flask, cool to 13°C, add 1.2g of cinchona base and 3.6g of diethylamine successively, stir for 15 minutes and pass Inject carbon dioxide gas and keep the temperature not higher than 20°C. React for 15 hours until carbon dioxide gas is no longer absorbed. The tert-butanol solvent was recovered by heatin...

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Abstract

The invention relates to a preparation method of (R)-propene carbonate, which comprises the following steps of: (1) mixing propylene oxide and epoxide hydrolase ECU1040 with water, carrying out reaction for 10-40 hours at the temperature of 0-5 DEG C, then, stopping the reaction, and distilling (R)-propylene oxide at normal atmosphere; and (2) mixing the obtained (R)-propylene oxide with an organic solvent, adding quinine and organic amine, leading in carbon dioxide gas at the temperature of 10-30 DEG C while stirring until the carbon dioxide gas is not absorbed, carrying out reaction for a total reaction time of 15-30 hours, and then obtaining the (R)-propene carbonate. The preparation method is simple and practical, the sources of the raw materials are wide, the reaction is carried out at the normal pressure, the risk is low, the equipment investment is small, the yield is high, the optical purity of the product reaches over 99% e.e, and thus, the preparation method has an excellentindustrial prospect.

Description

technical field [0001] The invention belongs to the field of preparation of tenofovir intermediates, in particular to a preparation method of (R)-propylene carbonate. Background technique [0002] (R)-Propylene carbonate is a key intermediate in the synthesis of anti-AIDS Tenofovir. In recent years, the following two methods have been used to produce (R)-propylene carbonate at home and abroad. The first method: obtain (R)-1,2-propanediol by hydrolysis and resolution of racemic propylene oxide, and then react with diethyl carbonate to produce the product. The second method: obtain (R)-propylene oxide from racemic propylene oxide by hydrolysis resolution, and then react with carbon dioxide to produce the product. [0003] The first method consumes a large amount of diethyl carbonate, and the raw material cost is high. The second method is relatively low cost of raw materials. However, it needs to be synthesized under 30 atmospheres in production, which requires high equipm...

Claims

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Application Information

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IPC IPC(8): C07D317/36
Inventor 李海林王世运张爱强张建现詹平平陈林
Owner 上海科利生物医药有限公司
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