Unlock instant, AI-driven research and patent intelligence for your innovation.

The preparation method of benzofuran derivative

A technology of benzofuran and its derivatives, which is applied in the field of organic compound synthesis, can solve the problems of complex preparation methods and low yields, and achieve the effects of cheap raw materials, simplified reaction steps, and avoiding low-temperature reactions

Active Publication Date: 2021-08-31
SHANGHAI HAOYUAN CHEMEXPRESS
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] The purpose of the present invention is to provide a preparation method of benzofuran derivatives, and further to provide a preparation method of 6-carboxylic acid benzofuran and pharmaceutically acceptable compounds thereof, so as to solve the problems in the prior art that the yield is low and the preparation complex technical issues

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
  • The preparation method of benzofuran derivative
  • The preparation method of benzofuran derivative
  • The preparation method of benzofuran derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Preparation of 6-carboxylic acid benzofuran

[0066]

[0067] 1. Add compound I (200kg, 1450mol, 1.0eq) and methanesulfonic acid (1000L) into a clean reactor, and stir to mix. Add compound II (305kg, 2170 mol, 1.5eq) in batches to the reaction flask, control the reaction temperature within 80°C, heat at 80°C after the addition, and stir for 3 hours. The starting material was consumed by TLC analysis. The temperature of the reaction solution was lowered to 50° C., 1500 L of pure water was added, and the mixture was stirred at room temperature for 1 hour after adding water. Extract the product with EA:MeOH (10:1) (500L x 6), combine the organic phases, and wash with saturated brine (300L x 2). Anhydrous sodium sulfate (20 kg) was dried and filtered to remove sodium sulfate. The organic phase was extracted with 10% NaOH aqueous solution (300L x 4), and the aqueous phase was combined, and the pH value of the aqueous phase was adjusted to about 3-4 with concentrated hy...

Embodiment 2

[0077]

[0078] Add compound IV to the reaction kettle 2 (8.6kg, 44.41mol, 1.0eq), compound Ⅴ (29.05 kg, 66.61mol, 1.5eq) and THF (80L), nitrogen protection. Cool down to 0°C, add sodium methoxide (3.97kg, 73.61mol, 1.65eq) THF solution (1M) dropwise to the reactor, control the temperature at 0-5°C, stir for 30min, continue to dropwise add sodium methoxide ( 1.30kg, 24.06mol, 0.54eq) THF solution (1M), temperature controlled at 0-5°C, stirred for 1 hour. According to TLC analysis, the consumption of raw materials was complete, and 200 L of petroleum ether was added to the reaction solution to quench the reaction. Then add 200L of petroleum ether, and filter the insoluble matter. Concentrate to obtain an oily liquid, disperse it with 200 L of petroleum ether, and filter the reaction liquid. The filter cake was beaten with petroleum ether (200L x 2), and the organic phases were combined and concentrated to dryness. Continue to disperse 50L with petroleum ether, filter to ...

Embodiment 3

[0080]

[0081] Add compound IV to the reaction kettle 3 (9.41kg, 44.41mol, 1.0eq), compound Ⅴ (29.05kg, 66.61mol, 1.5eq) and THF (80L), nitrogen protection. Cool down to 0°C, dropwise add a THF solution (1M) of potassium tert-butoxide (8.26kg, 73.61mol, 1.65eq) into the reaction kettle, control the temperature at 0-5°C, stir for 30min, continue to add tert-butoxide dropwise into the reaction kettle Potassium butoxide (2.70kg, 24.06mol, 0.54eq) THF solution (1M) was stirred at a temperature of 0-5°C for 1 hour. According to TLC analysis, the consumption of raw materials was complete, and 200 L of petroleum ether was added to the reaction solution to quench the reaction. Then add 200L petroleum ether, and filter the insoluble matter. Concentrate to obtain an oily liquid, disperse it with 200 L of petroleum ether, and filter the reaction liquid. The filter cake was beaten with petroleum ether (200L x 2), and the organic phases were combined and concentrated to dryness. Co...

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 discloses a preparation method for synthesizing benzofuran derivatives. The specific implementation method is as follows. The synthesis route of the invention is novel, easy to operate, high in yield and good in safety, and is suitable for industrial production. Among them, a new synthesis method of intermediate VI was also designed, and the wittig reaction was carried out, followed by ring closure to obtain the benzofuran ring.

Description

technical field [0001] The invention relates to the technical field of organic compound synthesis, in particular to a preparation method of benzofuran compounds. Background technique [0002] Benzofuran compounds have a variety of good physiological activities, such as antitumor, antibacterial, and antioxidative effects, and have attracted widespread attention. Benzofuran compounds are important frameworks for the synthesis of natural products and pharmaceuticals. For example, lifitegrast, a new type of small-molecule integration inhibitor, can be used to treat chronic ocular inflammatory diseases, which was approved by the FDA on July 11, 2016. [0003] The structure of Litahast is shown below: [0004] [0005] As an important intermediate of pharmaceutical composition, the synthesis of 6-carboxylic acid benzofuran (compound VII) is difficult. Currently published synthesis methods mainly include the following. [0006] Patent EP 816348 discloses a preparation method...

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 Patents(China)
IPC IPC(8): C07D307/79
CPCC07D307/79
Inventor 郑保富高强李硕梁杨成武马振标
Owner SHANGHAI HAOYUAN CHEMEXPRESS