A kind of recovery method and application of L-methyldopa intermediate

A technology for methyldopa intermediates and recovery methods, applied in organic chemistry methods, chemical instruments and methods, organic racemization, etc., can solve problems that have not been reported in literature, and achieve strong operability and easy process implementation and the effect of simple production and preparation methods

Active Publication Date: 2017-12-12
ZHEJIANG WILD WIND PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0021] In the present technology, although the preparation method of L-3-(3,4-dimethoxyphenyl)-2-methylalanine hydrochloride and L-methyldopa has more patent documents and papers Public reports have been carried out, but about recovering and synthesizing L-methyldopa from the mother liquor synthesized from L-3-(3,4-dimethoxyphenyl)-2-methylalanine hydrochloride, no other There are literature reports

Method used

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  • A kind of recovery method and application of L-methyldopa intermediate
  • A kind of recovery method and application of L-methyldopa intermediate
  • A kind of recovery method and application of L-methyldopa intermediate

Examples

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preparation example

[0039] 1) Synthesis of DL-aminopropionitrile

[0040] Dissolve 154.5g (3.15mol) 96%~98% sodium cyanide and 163g (3.05mol) ammonium chloride in 2200ml (26.8mol) of 12.2mol / L ammonia solution at room temperature, heat to 55℃, and stir quickly Quickly add 582.6g (3mol) of veratrone, stir for 1h, and then cool to below 20℃ within 1.5h, fine particles begin to separate out, keep stirring for 2h, cool to 0℃, filter with suction, the filtrate is DL-amino The mother liquor of propionitrile synthesis, the filter cake is washed with 800ml ice water, and dried to obtain 618.42g (2.81mol) of DL-aminopropionitrile. The molar yield is 93.7%. The melting point is 85℃~87℃. The obtained DL-aminopropionitrile is not Purification and direct resolution.

[0041] 2) Resolution of DL-aminopropionitrile

[0042] Dissolve 125g D-tartaric acid (0.83mol) in 500ml water, adjust the pH to 8 with sodium hydroxide to obtain D-tartaric acid disodium salt solution, add 4375ml water, 125g D-tartaric acid, 204.5g c...

Embodiment 1

[0051] Take 262.5ml of mother liquor obtained in step 4) (containing 10.67g of 3-(3,4-dimethoxyphenyl)-2-methylalanine hydrochloride), and add 32.8g of ammonium sulfate (volume to weight ratio of mother liquor) :Salt=8:1), carry out 60℃, vacuum-0.08mpa vacuum distillation, distill 168ml of water (COD:798mg / L), a small amount of crystals will precipitate out, cool to 0℃, filter, add 10ml ice water (0℃) ) Wash to obtain a solid, dry to obtain 9.7g, 3-(3,4-dimethoxyphenyl)-2-methylalanine hydrochloride, the recovery rate is 90.9%, and the HPLC purity is 98.3%; the mother liquor continues to be distilled Distilled water 30ml (COD: 839mg / L), a large number of crystals precipitated, cooled to 0°C, filtered to obtain a solid, dried to obtain 44.1g, containing COD: 1.2g, mother liquor 14ml, COD: 40936mg / L.

Embodiment 2

[0053] Take 262.5ml of mother liquor obtained in step 4) (containing 10.67g of 3-(3,4-dimethoxyphenyl)-2-methylalanine hydrochloride), add 21.8g of ammonium chloride (volume to weight ratio Mother liquor: salt=12:1), carry out 60℃, vacuum-0.08mpa vacuum distillation, distill 200ml of water (COD: 796mg / L), cool to 0℃, filter to obtain solid, dry 10.1g, 3-( The recovery rate of 3,4-dimethoxyphenyl)-2-methylalanine hydrochloride was 95%, and the purity by HPLC was 98.3%; the mother liquor continued to be distilled, and 34ml of water was distilled. A large amount of crystals precipitated, and the temperature was reduced to 0°C , Filtered to obtain solid, dried to obtain 34.2g, containing COD: 0.98g, mother liquor 10.8ml, COD: 23578mg / L

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Abstract

The invention discloses a recycling method and application of an L-methyldopa intermediate. The recycling method comprises the following steps: hydrolyzing L-3-(3,4-dimethoxy phenyl)-2-amino-2-methyl propionitrile hydrochloride by utilizing hydrochloric acid, and filtering to obtaining L-3-(3,4-dimethoxy phenyl)-2-methyl alanine hydrochloride and mother liquor, adding haloid salt or ammonium salt into the mother liquor, carrying out vacuum distillation, concentrating until volume is less than or equal to 1 / 3 of the original volume, and filtering, wherein a filter cake is namely the recycled 3-(3,4-dimethoxy phenyl)-2-methyl alanine hydrochloride solid. The recycling method disclosed by the invention has the advantages that L-methyldopa can be recycled from 3-(3,4-dimethoxy phenyl)-2-methyl alanine hydrochloride production waste liquor, and ammonia nitrogen and COD in wastewater can also be reduced, so that the recycling method accords with the green chemistry concept.

Description

Technical field [0001] The invention belongs to the technical field of drug synthesis, and specifically relates to a method and application for recovering L-methyldopa intermediates. Background technique [0002] L-Methyldopa is a receptor-blocking cardiovascular drug. It has a good effect on the treatment of moderate primary and secondary renal hypertension. It was listed as one of the national essential drugs by China in 1998. Therapeutic drugs are recommended for hypertension during pregnancy. Carbidopa is a dopa decarboxylic acid inhibitor. Because it cannot penetrate the blood-brain barrier, it only inhibits the conversion of peripheral levodopa into dopamine, which increases the amount of levodopa into the brain and reduces adverse reactions caused by peripheral dopamine. , So that the content of levodopa in the circulation increases. As more levodopa enters the brain, levodopa enters the brain center and is converted into dopamine, increasing the concentration of dopamin...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C227/18C07C229/36C07C227/34C07C227/16C07B57/00
CPCC07B57/00C07B2200/07C07C227/16C07C227/18C07C227/34C07C229/36
Inventor 周卫国张拥军曹铭红唐国军朱勇华胡伟强吴国英
Owner ZHEJIANG WILD WIND PHARMA
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