Synthetic method of bifendate intermediate

A technology for the synthesis of biphenyl diester and its synthetic method, which is applied in the field of synthesis of biphenyl diester intermediates, can solve the problems of restricting industrial production, incomplete protection, and difficult treatment, and achieve the solution of waste water problems, easy operation, and reduction of industrial waste water The effect of the treatment

Active Publication Date: 2020-04-14
苏州诚和医药化学有限公司
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The method uses borax to protect the methylation process, the protection is incomplete, polymethylated impurities are produced, the yield is low, and a large amount of borax-containing wastewater is produced, which is difficult to handle. Because the method mainly has the following shortcomings, it seriously restricts industrial production

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
  • Synthetic method of bifendate intermediate
  • Synthetic method of bifendate intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] A kind of synthetic method of bifendate intermediate, such as figure 2 shown, including the following steps:

[0027] 1. Synthesis of carbonate:

[0028] Add 20g (117.6mmol) of gallic acid (117.6mmol), 100ml of dichloromethane, 1g of triethylamine, 15g (141.1mmol) of sodium carbonate, and 30ml of water into the reaction flask, and add 14g (47.2mmol) of solid phosgene dropwise under stirring at a temperature of 15°C. After adding dichloromethane solution, keep warm at 15°C for 1 hour, let stand to separate the upper aqueous layer, concentrate the organic layer to dryness, add 100ml of toluene, stir for 30 minutes, filter, and dry to obtain 21.9g of carbonate, yield: 95%.

[0029] 2. Synthesis of methyl compounds:

[0030] Add 20g (102.0mmol) of carbonate, 100ml of acetone, and 31g (224.6mmol) of potassium carbonate into the reaction flask, add 28.3g (224.6mmol) of dimethyl sulfate dropwise at a controlled temperature of 25°C, and keep the temperature at 25°C for 5 ho...

Embodiment 2

[0037] A kind of synthetic method of bifendate intermediate, such as figure 2 shown, including the following steps:

[0038] 1. Synthesis of carbonate:

[0039] Add 20g (117.6mmol) of gallic acid (117.6mmol), 100ml of dichloromethane, 1g of triethylamine, 15g (141.1mmol) of sodium carbonate, and 30ml of water into the reaction flask, and add 11.2g (37.8mmol) of solid phosgene dropwise under stirring at a temperature of 10°C Dichloromethane solution, after adding, keep warm at 10°C for 1 hour, let stand to separate the upper aqueous layer, concentrate the organic layer to dryness, add 100ml of toluene, stir for 30 minutes, filter, and dry to obtain 22.0g of carbonate, the yield : 95.5%.

[0040] 2. Synthesis of methyl compounds:

[0041] Add 20g (102.0mmol) of carbonate, 100ml of acetone, and 35.2g (255.2mmol) of potassium carbonate into the reaction flask, add 32.2g (255.2mmol) of dimethyl sulfate dropwise at a controlled temperature of 20°C, and keep warm at 20°C for 4 ho...

Embodiment 3

[0048] A kind of synthetic method of bifendate intermediate, such as figure 2 shown, including the following steps:

[0049] 1. Synthesis of carbonate:

[0050]Add 20g (117.6mmol) of gallic acid (117.6mmol), 100ml of dichloromethane, 1g of triethylamine, 15g (141.1mmol) of sodium carbonate, and 30ml of water into the reaction bottle, and add 16.8g (56.6mmol) of solid phosgene dropwise under stirring at a temperature of 12°C After adding dichloromethane solution, heat it at 12°C for 1 hour, let it stand to separate the upper aqueous layer, concentrate the organic layer to dryness, add 100ml of toluene, stir for 30 minutes, filter, and dry to obtain 22.2g of carbonate, the yield : 96%.

[0051] 2. Synthesis of methyl compounds:

[0052] Add 20g (102.0mmol) of carbonate, 100ml of acetone, and 28.2g (204.2mmol) of potassium carbonate to the reaction flask, add 25.7g (204.2mmol) of dimethyl sulfate dropwise at a controlled temperature of 22°C, and keep warm at 22°C for 4.5 hour...

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

No PUM Login to view more

Abstract

The invention belongs to the field of chemical pharmacy, and particularly discloses a synthesis method of a bifendate intermediate, and the method comprises the following steps: by using gallic acid as a raw material, carrying out esterification reaction with solid phosgene to protect o-diphenolic hydroxyl, carrying out dimethylation and deprotection, and carrying out bromination and methylenationto obtain the bifendate intermediate. According to the synthetic method of the bifendate intermediate, the phosgene is adopted to protect the o-diphenolic hydroxyl, protection is complete, reaction conditions are mild, the process is simple, and operation is convenient. By exploring and optimizing conditions, the product yield and purity are high, the wastewater problem in a borax protection method is solved, the environment is not damaged, the later industrial wastewater treatment is reduced, the production cost of the whole process is reduced to the maximum extent, and the method has extremely high application value.

Description

technical field [0001] The invention belongs to the field of chemical pharmacy, and in particular relates to a method for synthesizing a bifendate intermediate. Background technique [0002] Biphenyldicarboxylate (Biphenyldicarboxylate, DDB) is an intermediate product of artificial synthesis of Schisandra C, a new drug discovered in the process of researching the traditional Chinese medicine Schisandra, clinically used for chronic persistent hepatitis with elevated alanine aminotransferase (ALT), It can also be used for ALT elevation caused by chemical poisons and drugs. [0003] CN86107486A discloses a synthetic method of biphenyl diester, the key intermediate of which is 2-bromo-3,4-methylenedioxy-5-methoxybenzoic acid methyl ester. The current industrial production process uses gallic acid as raw material , first esterify in methanol to obtain the methyl ester, then methylate under the protection of borax, and then obtain the target intermediate through bromination and c...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D317/68
CPCC07D317/68
Inventor 陈晓强
Owner 苏州诚和医药化学有限公司
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