Environmental protection preparation method of (R)-(-)-4-cyano-3-hydroxy ethyl butyrate

A green and environmentally friendly technology of ethyl hydroxybutyrate, which is applied in the fields of medicine and chemical industry, can solve the problems of poor atom economy, high preparation cost, and low yield, and achieve the effects of low production cost, simple preparation process, and few by-products

Pending Publication Date: 2019-04-16
抚顺顺能化工有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Aiming at the technical problems of high preparation cost, heavy pollution, poor atom economy and low yield of (R)-(-)-4-cyano-3-hydroxybutyric acid ethyl ester existing in the prior art, the present invention provides A kind of preparation method of (R)-4-cyano-3-hydroxybutyric acid ethyl ester which is green, low-cost, high-yield, simple process and suitable for industrial production is proposed, and the technical scheme adopted is as follows;

Method used

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  • Environmental protection preparation method of (R)-(-)-4-cyano-3-hydroxy ethyl butyrate

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Experimental program
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Effect test

Embodiment 1

[0066] Embodiment 1 prepares (S)-(-)-4-chloro-3-hydroxybutyronitrile

[0067] Add 100g (1.08mol) (S)-epichlorohydrin, 200g water and 2g diethylamine into a 1000mL three-necked flask at one time, stir and mix for 5min to obtain a mixed solution, and drop 1-2 drops per second under the condition of 20°C Add 37.9g ​​(1.40mol) of liquid hydrocyanic acid to the above-mentioned mixed solution at a speed of 20°C, continue stirring and reacting for 10h to obtain a reaction solution, adjust the pH value of the reaction solution to 5 with 50% sulfuric acid, and distill under reduced pressure Remove water, then high vacuum rectification obtains 119.6g content 99.14% (specific rotation [α] D 25 =-16.8°) of (S)-(-)-4-chloro-3-hydroxybutyronitrile, yield 92.71%.

Embodiment 2

[0068] Embodiment 2 prepares (S)-(-)-4-chloro-3-hydroxybutyronitrile

[0069] Add 100g (1.08mol) (S)-epichlorohydrin, 200g water and 2g diethylamine into a 1000mL three-neck flask at one time, stir and mix for 5 minutes to obtain a mixed solution, and at 25°C, 1-2 drops per second Add 43.8g (1.62mol) of liquid hydrocyanic acid to the above-mentioned mixed solution at a speed of 25°C, continue to stir and react for 6h to obtain a reaction solution, adjust the pH value of the reaction solution to 5 with 50% sulfuric acid, and distill under reduced pressure Remove water, then high vacuum rectification obtains 122.5g content 99.34% (specific rotation [α] D 25 =-17.0°), (S)-(-)-4-chloro-3-hydroxybutyronitrile, yield 94.96%.

Embodiment 3

[0070] Embodiment 3 prepares (S)-(-)-4-chloro-3-hydroxybutyronitrile

[0071] Add 100g (1.08mol) (S)-epichlorohydrin, 200g water and 2g diethylamine into a 1000mL three-neck flask at one time, stir and mix for 5 minutes to obtain a mixed solution, and at 25°C, 1-2 drops per second Add 30% sodium cyanide solution and 50% sulfuric acid to the above-mentioned mixed solution at the same speed, continue to stir and react for 12 hours at 25°C to obtain a reaction solution, adjust the pH value of the reaction solution to 5 with 50% sulfuric acid, reduce Press distillation to remove water, filter to remove salt, then high vacuum rectification to obtain 105g content 99.06% (specific rotation [α] D 25 =-16.9°) of (S)-(-)-4-chloro-3-hydroxybutyronitrile, yield 81.26%.

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Abstract

The invention discloses an environmental protection preparation method of (R)-(-)-4-cyano-3-hydroxy ethyl butyrate and belongs to the technical field of medicine and chemical industry. The method comprises the following steps of: using (S)- epichlorohydrin as a start material, carrying out nucleophilic addition reaction on the epichlorohydrin and liquid hydrocyanic acid under the catalysis of alkali to obtain (S)-(-)-4-chlorine-3-hydroxybutyronitrile; carrying out Pinner reaction on the (S)-(-)-4-chlorine-3-hydroxybutyronitrile and hydrogen chloride-ethanol to obtain a hydrochloride intermediate of urethane, and then hydrolyzing the intermediate to obtain (S)-(-)-4-chlorine-3-ethyl hydroxybutyrate; finally, reacting (S)-(-)-4-chlorine-3-ethyl hydroxybutyrate and hydrocyanic acid and ammonia water under the analysis of biological enzyme to prepare the (R)-(-)-4-cyano-3-hydroxy ethyl butyrate. In the whole synthesis process of the method, other organic solvents other than water are not used, the reaction condition is mild, the process is simple, the chemical purity and optical purity of the product are higher, no waste water, waste salt or waste gas is generated in the whole process,the method achieves win-win of economic benefit and environmental benefit and is favorable for achieving large-scale industrial production.

Description

technical field [0001] The invention relates to a green and environment-friendly preparation method of ethyl (R)-(-)-4-cyano-3-hydroxybutyrate, which belongs to the technical field of medicine and chemical industry. Background technique [0002] Statins are currently the main lipid-lowering drugs, and their lipid-lowering effects are mainly manifested in the inhibition of 3-hydroxy-3-methyl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the process of cholesterol biosynthesis. , reduce intracellular free cholesterol, accelerate the clearance of very low-density lipoprotein (VLDL) remnants (IDL) and low-density lipoprotein (LDL) in circulation, and finally reduce the level of total cholesterol and LDL in serum. Atorvastatin is a new type of high-efficiency statin drug developed by Warner-Lambert Company of the United States. It has become a leader in blood lipid-lowering drugs because of its safety and high efficiency. Atorvastatin is mainly composed of a core a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P13/00
CPCC12P13/002
Inventor 周怡胡成楠王晓宁胡德启张雪
Owner 抚顺顺能化工有限公司
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