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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
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  • 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.
[0021] In the prior art, although the preparation method of veratrone and L-methyldopa has more patents and literatures to carry out public reports, but about the recovery of veratrone, especially from the production waste liquid of L-methyldopa Recovery of veratrone, there is no literature report

Method used

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  • Preparation method of L-methyldopa
  • Preparation method of L-methyldopa
  • Preparation method of L-methyldopa

Examples

Experimental program
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Effect test

Embodiment 1

[0054] 1) Synthesis of DL-aminopropionitrile

[0055] Dissolve 515g (3.15mol) of 30% sodium cyanide aqueous solution and 163g (3.05mol) of ammonium chloride in 2200ml (23.3mol) of 10.6mol / L ammonia solution at room temperature, heat to 55°C, and rapidly stir Add 582.6g (3mol) veratrone, stir for another 1h, then cool down to 20°C-25°C in 1-1.5h, the product with fine particles begins to precipitate, keep stirring for 2h, cool down to 0°C and filter with suction, 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 (94.3% molar yield), with a melting point of 85°C to 87°C. The obtained DL-aminopropionitrile can be directly resolved without purification.

[0056] 154.5g (3.15mol) 96%~98% sodium cyanide and 160.5g (3mol) ammonium chloride room temperature are dissolved in the mother liquor that the DL-aminopropionitrile that the last step of 2089ml ...

Embodiment 2

[0076] Add 2089ml of DL-aminopropionitrile synthesis mother liquor (COD: 48271ppm, pH=10.5) obtained in step 1) of Example 1 to the reaction flask, add 600ml of dichloroethane, stir and heat up to reflux, reflux for 5h, After the reaction was completed, cool to room temperature, let stand to separate layers, and extract the water layer with 300ml dichloroethane again to obtain a water layer and an organic layer;

[0077] COD detected in the water layer: 13567ppm, most of which are caused by dichloroethane dissolved in water. After aeration for 5 hours, the detected COD: 4368ppm, the COD removal rate is 91%. The COD is passed through the COD rapid detector, using the national general standard;

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

Embodiment 3

[0080] Add 1500ml of DL-aminopropionitrile synthesis mother liquor (COD: 46638ppm, pH=10.3) obtained in step 1) of Comparative Example 1 to the reaction flask, add 300ml of dichloromethane, stir and heat up to reflux, reflux for 12h, cool after the reaction is completed to room temperature, standing and stratifying to obtain an aqueous layer and an organic layer;

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

[0082] After the organic layer was distilled to recover the solvent, high vacuum distillation (the pressure of high vacuum distillation was 2mmHg, 0.266kPa), collected 20.2g of cuts at 112°C to 120°C, and gas chromatography (GC) detected that the content of veratrone was 98.86%. The rutrune content was obtained by the are...

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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

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Application Information

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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
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