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

Preparation method of bromomethyl cyclobutane

A technology of bromomethylcyclobutane and cyclobutane, which is applied in the field of preparation of analgesic drug intermediates, can solve the problems of high environmental protection pressure and high cost, and achieve the effects of easy operation, cheap raw materials, and mild reaction conditions

Inactive Publication Date: 2013-12-11
HONGSHENG SCI TECH DEV
View PDF0 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, chloroform, a toxic solvent such as chloroform, is used in the post-treatment, which poses a great pressure on environmental protection, and the cost of the product is still high due to the use of lithium reagents.

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
  • Preparation method of bromomethyl cyclobutane

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Add 86g of cyclobutanol (1mol), 372g (1.2mol) of triphenyl phosphite and 860mL of dichloromethane into a 2-liter reaction flask equipped with a stirrer and a thermometer, and add 214g of bromosuccinyl in batches under stirring Imine (1.2mol), control the reaction temperature at 38±2°C, after the addition, continue to stir at constant temperature for 4 hours. After the reaction is completed, the organic phase is washed with water four times, each time with 50 mL of water, and then concentrated by atmospheric distillation. After the dichloromethane has been removed, it is then distilled under reduced pressure. Rectification, cooling the condenser with ice water, collecting the fraction at 134-136°C to obtain 108g of bromomethylcyclobutane, that is, the yield is 72%, and analyzed by liquid chromatography, the purity of the prepared bromomethylcyclobutane is 98.3%.

Embodiment 2

[0029] Add 430g cyclobutanol (5mol), 1706g (5.5mol) of triphenyl phosphite and 4L dichloromethane into a 10-liter reaction flask equipped with a stirrer and a thermometer, and add 979g bromosuccinyl in batches under stirring Imine (5.5mol), control the reaction temperature at 35±2°C, after the addition, continue to stir at constant temperature for 6 hours. After completion of the reaction, the organic phase was washed with water four times, each time with 1500 mL of water, then distilled at atmospheric pressure, then distilled under reduced pressure, cooled the condenser with ice water, collected all the cuts, then carried out rectification at normal pressure, cooled the condenser with ice water, The fractions at 134-136°C were collected to obtain 559g of bromomethylcyclobutane, that is, the yield was 75%. Through liquid chromatography analysis, the purity of bromomethylcyclobutane was 98.6%.

Embodiment 3

[0031] Add 86g of cyclobutanemethanol (1mol), 573g (1.5mol) of monophenylenedioctyl phosphite (1.5mol) and 600mL of diethyl ether into a 2-liter reaction flask equipped with a stirrer and a thermometer, and add 515g of dibromohydantoin in batches under stirring (1.8mol), control the reaction temperature at 38±2°C, after the addition, continue to stir at constant temperature for 4 hours. After the reaction is complete, the organic phase is washed four times with 50 mL of water each time, and then concentrated by atmospheric distillation. After the ether has been removed, it is then distilled under reduced pressure, and the condenser is cooled with ice water. All fractions are collected, and then subjected to atmospheric distillation. , cooling the condensing tube with ice water, collecting the distillate at 134-136°C to obtain 109g of bromomethylcyclobutane, that is, the yield was 73%, and analyzed by liquid chromatography, the purity of bromomethylcyclobutane was 98.2 %.

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 preparation method of an analgesic drug intermediate, particularly relates to a preparation method of bromomethyl cyclobutane and aims at providing the preparation method of the bromomethyl cyclobutane, which is easy to operate and low in cost. The preparation method of the bromomethyl cyclobutane comprises the following steps: a, adding cyclobutyl methanol into an aprotic solvent, and adding phosphite ester with a benzene ring structure; b, adding a brominating agent in batches, controlling the reaction temperature to 20 DEG C-40 DEG C and stirring for 1-6 hours; and c, washing, organic-phase drying and distilling to obtain bromomethyl cyclobutane. According to the preparation method of the bromomethyl cyclobutane disclosed by the invention, the materials are cheap and easily available, the preparation method does not need refrigeration, the reaction conditions are gentle, the process is simple, and the operation is easy, and therefore, the preparation method is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of an analgesic drug intermediate, in particular to a preparation method of bromomethylcyclobutane. Background technique [0002] After the introduction of cyclobutylmethyl on the nitrogen atom of the opioid molecule, an analgesic with both agonistic and antagonistic effects on opioid receptors can be produced, and the addiction is greatly reduced. For example, the analgesic effect of butorphanol is that of morphine. 3-4 times, less addictive, has been collected in the United States Pharmacopoeia. The analgesic effect of Nadine is similar to that of morphine, but the side effects and addiction are very small. Bromomethylcyclobutane is an important intermediate in the synthesis of such analgesic drugs. [0003] There are few reports on the preparation method of bromomethylcyclobutane. According to the literature, the synthesis method of bromomethylcyclobutane in the prior art is mainly prepared by brominat...

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): C07C22/00C07C17/16
Inventor 曾彪
Owner HONGSHENG SCI TECH DEV
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