Preparation method of L-methyldopa

A technology of L-methyldopa and racemization, which is applied in the field of preparation of L-methyldopa, can solve the problems of polluting the environment, increasing the cost of three wastes, and no literature reports about it, and achieves simple treatment methods and molar total Increased yield and good environmental benefits

Inactive Publication Date: 2012-07-04
ZHEJIANG CHIRAL MEDICINE CHEM
View PDF1 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The waste liquid after the separation of DL-aminopropionitrile is recovered by distillation to recover the solvent. Most of the residual liquid after recovering the solvent is organic matter, which is usually incinerated, which increases the cost of three wastes and pollutes the environment.
[00

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of L-methyldopa
  • Preparation method of L-methyldopa
  • Preparation method of L-methyldopa

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0053] Example 1

[0054] 1) Synthesis of DL-aminopropionitrile

[0055] 515g (3.15mol) of 30% sodium cyanide aqueous solution and 163g (3.05mol) of ammonium chloride were dissolved in 2200ml (23.3mol) of 10.6mol / L ammonia solution at room temperature, heated to 55°C, and rapidly stirred under rapid stirring. Add 582.6g (3mol) veratrolone, stir for another 1h, and then cool down to 20°C to 25°C in 1-1.5h, the product of fine particles begins to separate out, continue stirring for 2h, cool down to 0°C and suction filtration, the filtrate is DL- The mother liquor of aminopropionitrile synthesis (2089ml), the filter cake was washed with 800ml of ice water, and dried to obtain 623.17g of DL-aminopropionitrile (molar yield: 94.3%), the melting point was 85℃~87℃. The resulting DL-aminopropionitrile can be directly resolved without purification.

[0056] 154.5g (3.15mol) of 96%~98% sodium cyanide and 160.5g (3mol) ammonium chloride were dissolved in 2089ml of the synthetic mother l...

Example Embodiment

[0075] Example 2

[0076] To the reaction flask, add 2089ml of the mother liquor (COD: 48271ppm, pH=10.5) of the synthesis of DL-aminopropionitrile obtained in the first step of Example 1, step 1), add 600ml of dichloroethane, stir and heat up to reflux, reflux for 5h, After the reaction was completed, it was cooled to room temperature, left to stand for layers, and the aqueous layer was extracted once more with 300 ml of dichloroethane to obtain an aqueous layer and an organic layer;

[0077] Water layer detection COD: 13567ppm, most of which is caused by the dissolution of dichloroethane in water. After aeration for 5h, the detection COD: 4368ppm, the COD removal rate is 91%, the COD is through the COD rapid detector, using the national general standard;

[0078] The organic layers were combined, and after the solvent was recovered by distillation, high-vacuum distillation (the pressure of high-vacuum distillation was 2mmHg, 0.266kPa), the fraction 28.5 g at 112° C. to 120° ...

Example Embodiment

[0079] Example 3

[0080] 1500ml of the synthetic mother liquor (COD: 46638ppm, pH=10.3) of DL-aminopropionitrile obtained in step 1) of Comparative Example 1 was added to the reaction flask, 300ml of dichloromethane was added, the temperature was stirred and heated to reflux, refluxed for 12h, and cooled after the reaction was completed. to room temperature, stand for stratification to obtain an aqueous layer and an organic layer;

[0081] Water layer detection COD: 14639ppm, most of which is caused by the dissolution of dichloromethane in water. After aeration for 5h, the detection COD: 4691ppm, the COD removal rate is 90%, the COD is through the COD rapid detector, using the national general standard;

[0082] After the organic layer distillation reclaims the solvent, high-vacuum distillation (the pressure of high-vacuum distillation is 2mmHg, 0.266kPa), collects the fraction 20.2g of 112 ℃~120 ℃, gas chromatography (GC) detects and obtains veratrolone content is 98.86%, ve...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
Melting pointaaaaaaaaaa
Melting pointaaaaaaaaaa
Melting pointaaaaaaaaaa
Login to view more

Abstract

The invention discloses a preparation method of L-methyldopa. The key points of the method are as follows: veratone is recycled from the L-methyldopa production waste liquor, the mother liquor synthesized from DL-aminopropionitrile or the racemic mother liquor of D-aminopropionitrile is mixed with an organic solvent, the mixture is heated to 40-110 DEG C to react for 1-24 hours, and the obtained solution is stood and layered after the reaction to obtain a water layer and an organic layer; the organic solvent is a non-solvent of water and a good solvent of veratone; or alkali and water are added in the splitting waste liquor of DL-aminopropionitrile, the pH is adjusted to 7-14, the solution is heated to 40-110 DEG C to react for 1-24 hours, and the obtained solution is stood and layered after the reaction to obtain a water layer and an organic layer; and the solvent is recycled from the obtained organic layer, and high vacuum distillation is performed under the condition that the pressure is no more than 5kPa to obtain veratone for reuse. By adopting the preparation method of L-methyldopa, the main raw material veratone can be recycled from the L-methyldopa production waste liquor, the chemical oxygen demand (COD) of wastewater can be reduced and the concept of green chemistry can be realized.

Description

technical field [0001] The invention relates to the field of pharmaceutical chemical synthesis, in particular to a preparation method of L-methyldopa. Background technique [0002] Levomethyldopa is a receptor-blocking cardiovascular drug that has a good effect on the treatment of moderate primary and secondary renal hypertension. It is a Class B basic medical insurance product recommended by the United Nations and was approved in 1998. China listed it as one of the national essential medicines. Veratrone, whose chemical name is 3,4-dimethoxyphenylacetone, is the starting material for the synthesis of L-methyldopa, and veratrone reacts with sodium cyanide and ammonium chloride to generate DL-3-( 3,4-dimethoxyphenyl)-2-amino-2-methylpropionitrile, referred to as DL-aminopropionitrile, and then split and hydrolyzed to obtain L-methyldopa. [0003] The synthesis of L-methyldopa generally adopts the following route: [0004] 1) Synthesis of DL-3-(3,4-dimethoxyphenyl)-2-amino-...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07C229/36C07C227/30C07C49/255C07C45/80
Inventor 黄有明胡文钢孙文龙刘田春王永虹屠佳秋
Owner ZHEJIANG CHIRAL MEDICINE CHEM
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap