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

Anti-malaria medical raw material benflumetol intermediate 2,7-dichlorofluorene-4-ethylene oxide synthesis process

A technology of ethylene oxide and dichlorofluorene, applied in 2 fields, can solve the problems such as high price of bromoacetyl bromide, unenvironmental protection, unsuitable for industrialized production, etc., achieves green environmental protection production procedure, great economic and social benefits, and simple equipment Effect

Inactive Publication Date: 2013-11-27
ZHANG JIA GANG VINSCE BIO PHARM
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In a route for the synthesis of benzfluorenol reported by Deng Rongxian of the Academy of Military Medical Sciences, 2,7-dichlorofluorene-4-oxirane was synthesized in four steps using fine fluorene as a raw material, and the main intermediate products were 2,7- Dichlorofluorene, 2,7-dichloro-4-chloroacetyl fluorene and 2,7-dichloro-4-(2-chloroethanol) fluorene, this route is the common route of benzfluorenol manufacturers at home and abroad at present, However, the production process is relatively cumbersome and the production cost is relatively high.
[0006] In a synthesis route of benzfluorenol reported by Dong Liuyu, a graduate student of Wuhan University of Technology in his dissertation, 2,7-dichlorofluorene-4-oxirane was synthesized in four steps using fine fluorene as a raw material, and the main intermediate products were 2,7-dichlorofluorene, 2,7-dichloro-4-bromoacetyl fluorene and 2,7-dichloro-4-(2-bromoethanolyl) fluorene, bromoacetyl bromide, an important raw material for this route, is expensive , although the yield has increased, the overall cost of the synthesized intermediate 2,7-dichlorofluorene-4-oxirane is too high and is not suitable for large-scale industrial production
[0007] The above method has the following shortcomings in the synthesis of benzfluorenol key intermediate-2,7-dichlorofluorene-4-oxirane: (1) Synthetic 2,7-dichlorofluorene with simple chemical raw material o-aminobenzaldehyde -4-Ethylene oxide intermediate, the route is too long, the use of raw and auxiliary materials is too much, the chemical atom economy is not good, and it is not environmentally friendly
(2) The route reported by Deng Rongxian has many shortcomings such as excessive acylation catalyst, not green and environmentally friendly, and complicated process flow.
(3) The route reported by Dong Liuyu is similar to that of Deng Rongxian, but the key acylating agent used is different, and the acylating agent is expensive, which makes the overall cost of 2,7-dichlorofluorene-4-oxirane intermediate too high, while Not suitable for 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
  • Anti-malaria medical raw material benflumetol intermediate 2,7-dichlorofluorene-4-ethylene oxide synthesis process

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 12

[0021] Embodiment 12, the synthesis of 7-dichlorofluorene-4-oxirane intermediate

[0022] In a 3000L enamel reaction kettle, add 2000L of dichloromethane and anhydrous AlCl 3 25kg, stir and disperse, control the temperature of the ice-salt bath below 5°C, slowly add 160kg of chloroacetyl chloride, and stir for 1.5h for complexation, then slowly add 330kg of 2,7-dichlorofluorene in batches, the process control temperature is within 5°C, After reacting for 2 hours, the temperature was naturally raised to room temperature to continue the reaction for 2 hours until the raw material 2,7-dichlorofluorene was completely reacted as monitored by thin layer chromatography. Continue in the above-mentioned enamel reaction kettle, control the temperature within 10°C, add 140L of 10% NaOH solution, stir the reaction while adding, until the pH value is neutral, remove excess chloroacetyl chloride and neutralize excess AlCl 3 . Continue to add 2.5 kg of potassium borohydride in batches at r...

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 preparation of a key intermediate 2,7-dichlorofluorene-4-ethylene oxide of an anti-malaria medical raw material benflumetol. According to the synthesis process, in a single reaction kettle, 2,7-dichlorofluorene is adopted as a starting raw material, chlorine acetylation is catalyzed through a Lewis acid, metal borohydride reduction is performed, alkalization is performed to obtain an epoxide, and extraction separation, concentration crystallization and methanol or ethanol dispersion washing are performed after completing the reaction to obtain the high purity qualified product. The method has characteristics of simple process and simple operation, and is suitable for industrial production.

Description

technical field [0001] The present invention relates to the synthesis of 2,7-dichlorofluorene-4-oxirane, a key intermediate of benzfluorenol, an anti-malarial pharmaceutical raw material, and specifically relates to the synthesis of 2,7-dichlorofluorene-4-oxirane, which is a by-product of coal chemical industry, fluorene. -Dichlorofluorene, obtained by Lewis acid-catalyzed chloroacetylation, then alkalization to epoxide, crystallization from methanol or ethanol. Background technique [0002] 2,7-Dichlorofluorene-4-oxirane is a key intermediate in the synthesis of antimalarial drug lumefantrine. As a new mefloquine drug for the treatment of malaria developed in my country, it is mainly used clinically for a very serious tropical infectious disease. The disease has almost no patients in China, and it is mainly used in Africa, South America, and a few areas of Asia. In Africa, more than 3 million people die from malaria every year, mainly women and children. The characteristi...

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): C07D303/08C07D301/26
CPCY02A50/30
Inventor 彭学东张梅赵金召闫勇义
Owner ZHANG JIA GANG VINSCE BIO PHARM
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