Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Synthesis method of probucol

A synthesis method, the technology of probucol, applied in the field of synthesis of raw material probucol, can solve the problems of no product yield and purity, inaccurate yield data, low product purity, etc., to reduce product cost and high product purity , the effect of simple operation

Active Publication Date: 2013-06-12
山东安弘制药有限公司
View PDF5 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The reaction mechanism of this method is similar to method 1, and there are also situations where the yield is not high and the purity is insufficient
Although it is mentioned in CN10142348A that the yield can reach 90%, the yield data is not accurate because it is prepared by "one pot method", and there is no yield and purity of the product in its examples
According to the experimental verification, the yield of this step is actually only about 70% and the purity of the product obtained according to this method is low

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
  • Synthesis method of probucol
  • Synthesis method of probucol
  • Synthesis method of probucol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Raw material 2,6-di-tert-butyl-4-mercaptophenol solid (I) 47.7g (0.2mol), put it into a 0.5L autoclave, then add 76g methanol and 21.6g (0.40mol) sodium methoxide, heat Stir to dissolve at 50°C, continue heating to 60°C, pass in propyne, keep the pressure of 1MPa, stir and react for 3h, then release the pressure, transfer the liquid to a 500ml five-necked flask, add 2,6-di-tert 47.7g (0.2mol) of butyl-4-mercaptophenol, add 35% hydrochloric acid by mass concentration under stirring to make pH≤1, heat to 60-65℃, keep for 1h, then cool to 5-15℃, stir for 4-6h, filter with suction , The crude probucol was obtained, washed with water, then refined with 95% ethanol, and dried in vacuum to obtain 96.9 g of the pure probucol, with a total yield of 93.8% and an HPLC purity of 99.90%. mp125~126℃.

[0032] Product element analysis (%): the measured value C is 71.96, H is 9.44, S is 12.36; the theoretical value C is 72.04, H is 9.36, and S is 12.41. IR (KBr) cm-1: 3634, 3078, 2960, 2...

Embodiment 2

[0034] As described in Example 1, the difference is that the volume of the reactor used is doubled, and the influence of the amount of alkyne on the reaction is investigated.

[0035] Add 47.7g (0.2mol) of 2,6-di-tert-butyl-4-mercaptophenol into a 1.0L autoclave, add 76g of methanol and 21.6g (0.4mol) of sodium methoxide, heat to 50℃ and stir to dissolve the raw materials , Continue to heat to 60 ℃, pass in propyne, and maintain the pressure of 1 MPa, stir the reaction for 3 hours and release the pressure, transfer to a 500ml five-necked flask, and then add 2,6-di-tert-butyl-4-mercaptophenol 47.7 g(0.2mol), heat to 60℃ and stir to dissolve, add 35% hydrochloric acid by mass concentration to adjust pH=0.8, continue to heat to 60-65℃, keep for 1h, then cool to 5-15℃, stir for 4-6h, filter by suction and wash with water Then it was refined with 95% ethanol and dried in vacuum to obtain 97.6 g of probucol. The total yield was 94.5% and the HPLC purity was 99.93%.

Embodiment 3

[0037] As described in Example 2, the difference is that 110 g of ethanol is used instead of 76 g of methanol in Example 2, and 26.4 g (0.4 mol) of sodium ethoxide is used instead of sodium methoxide in Example 2. Finally, 94.0 g of probucol was obtained, the total yield was 90.9%, and the HPLC purity was 99.93%.

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 relates to a synthesis method of probucol. The method comprises the following steps of: reacting 2,6-di-tert-butyl-4-mercaptophenol used as a starting material with allylene through pressurization under the catalysis of alkaline conditions, and then reacting the obtained olefin intermediate with 2,6-di-tert-butyl-4-mercaptophenol under the catalysis of a strong acid so as to obtain a product probucol. The method disclosed by the invention is simple in operation, high in product yield and good in purity.

Description

Technical field [0001] The invention relates to a method for synthesizing raw material drug probucol, and belongs to the technical field of medicinal chemistry. Background technique [0002] Probucol (C 31 H 48 O 2 S 2 ) It has the effects of regulating blood lipids, preventing atherosclerosis and anti-lipid peroxidation. Its blood lipid-lowering and anti-oxidant effects are significant, and its side effects are small. [0003] At present, there are two main synthetic methods for Probucol: [0004] Method 1. Using 2,6-di-tert-butyl-4-mercaptophenol as a raw material, methanol is used as a solvent to condense with acetone under the catalysis of hydrochloric acid; the reaction conditions of this method are relatively mild, but the yield is low. CN1228419 reported this The yield of the method is only 70%, and the highest yield reported by US2008119672 and EP1849768 is only 82%. [0005] Method 2. Probucol is prepared by condensation of 2,6-di-tert-butyl-4-mercaptophenol and 2,2-dimethox...

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): C07C323/20C07C319/18
Inventor 杨英英汤沸刘朝建冯宪东赵卫良
Owner 山东安弘制药有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com