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

Preparation method of 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl) methyl] thiophene

A technology of methylphenyl and fluorophenyl, which is applied in the field of preparation of 2--5-[methyl]thiophene, can solve the problems of easy oxidation yield and difficult storage, and achieve high reaction yield and production The effect of low cost and less waste

Inactive Publication Date: 2015-01-28
SHANDONG UNIV
View PDF8 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The α, β unsaturated aldehydes used in this reaction have the problems of not being easy to store (easy to oxidize in air) and low yield

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 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl) methyl] thiophene
  • Preparation method of 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl) methyl] thiophene
  • Preparation method of 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl) methyl] thiophene

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] A preparation method of 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl)methyl]thiophene, comprising the following steps:

[0032] Step 1: Preparation of (5-nitro-2-methylphenyl)(5-bromo-2-thiophene)methanone (IV)

[0033]Take 5-nitro-2-methyl-benzoyl chloride (VI) (47mmol) and dissolve it in a mixed solvent of ethanol (45ml) and water (10ml), and add tris(dibenzylideneacetone) dipalladium (0.58 mmol), tricyclohexylphosphine (2.35mmol), potassium carbonate (47mmol) and 5-bromothiophene-2-boronic acid (VII) (23.5mmol), the reaction was stirred at 60°C for 20h, cooled to room temperature, and anhydrous Magnesium sulfate was used to remove the moisture in the system, ethyl acetate (20ml×3) was added to dissolve, magnesium sulfate was removed by filtration, the filtrate was collected and concentrated to obtain a crude product, which was added with ethanol (5ml) and recrystallized to obtain (5-nitro-2- Methylphenyl)(5-bromo-2-thiophene)methanone (IV) (90% yield).

[0034] 1...

Embodiment 2

[0045] Step 1: Preparation of (5-nitro-2-methylphenyl)(5-bromo-2-thiophene)methanone (IV)

[0046] Take 5-nitro-2-methyl-benzoyl chloride (VI) (47mmol) and dissolve it in a mixed solvent of ethanol (45ml) and water (10ml), and add tris(dibenzylideneacetone) dipalladium (0.50 mmol), tricyclohexylphosphine (2.35mmol), potassium carbonate (47mmol) and 5-bromothiophene-2-boronic acid (VII) (16mmol), stirred and reacted at 90°C for 24h, cooled to room temperature, and used excess anhydrous sulfuric acid Magnesium removed the water in the system, added ethyl acetate (20ml×3) to dissolve, filtered to remove magnesium sulfate, collected the filtrate and concentrated to obtain a crude product, added ethanol (5ml), and recrystallized to obtain (5-nitro-2-methyl phenyl)(5-bromo-2-thiophene)methanone (IV) (93% yield). Proton spectrum and mass spectrum data are the same as in Example 1, the same below.

[0047] Step 2: Preparation of (5-nitro-2-methylphenyl)(5-(4-fluorophenyl)-2-thiophen...

Embodiment 3

[0054] Step 1: Preparation of (5-nitro-2-methylphenyl)(5-bromo-2-thiophene)methanone (IV)

[0055] Take 5-nitro-2-methyl-benzoyl chloride (VI) (47mmol) and dissolve it in a mixed solvent of ethanol (45ml) and water (10ml), and add tris(dibenzylideneacetone) dipalladium (0.65 mmol), tricyclohexylphosphine (2.0mmol), potassium carbonate (42mmol) and 5-bromothiophene-2-boronic acid (VII) (40mmol), stirred and reacted at 60°C for 24h, cooled to room temperature, and used excess anhydrous sulfuric acid Magnesium removed the water in the system, added ethyl acetate (20ml×3) to dissolve, filtered to remove magnesium sulfate, collected the filtrate and concentrated to obtain a crude product, added ethanol (5ml), and recrystallized to obtain (5-nitro-2-methyl phenyl)(5-bromo-2-thiophene)methanone (IV) (yield 79%).

[0056] Step 2: Preparation of (5-nitro-2-methylphenyl)(5-(4-fluorophenyl)-2-thiophene)methanone (III)

[0057] Get (5-nitro-2-methylphenyl) (5-bromo-2-thiophene) ketone (...

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 of 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl) methyl] thiophene. The 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl) methyl] thiophene is prepared by performing twice Suzuki cross-coupling reactions between 5-nitro-2-methyl-benzoyl chloride and 5-bromothiophene-2-boronic acid first and then between a reaction product and 4-fluorophenylboronic acid, a reducing reaction and a Sandmeyer reaction. The preparation method belongs to the field of preparation of medicine intermediates. The preparation method can be used for preparing a medicine Invokana for treating type-II diabetes. The preparation method has the characteristics of simple operation, good process stability, high yield, few solid, liquid and gas wastes, low production cost and good product quality.

Description

technical field [0001] The invention relates to a preparation method of 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl)methyl]thiophene, which belongs to the field of preparation of pharmaceutical intermediates. Background technique [0002] 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl)methyl]thiophene is a drug intermediate for the synthesis of canagliflozin. Mitsubishi Tanabe Pharmaceutical Co., Ltd. discloses its method of synthesizing canagliflozin as an intermediate in multiple patents such as CN200480022007.8, CN200980151648.6, CN201310090402.0, and CN201310358939.0. [0003] The synthetic method of 2-(4-fluorophenyl)-5-[(5-bromo-2-methylphenyl)methyl]thiophene currently has the following approaches: [0004] (1) Friedel-Crafts reaction. The typical way of this reaction is that 2-substituted thiophene and acyl halide or acid anhydride are condensed under the catalysis of anhydrous AlCl3 to generate thiophene with substituent in 2 and acyl in 5, as in CN200980151648.6...

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): C07D333/12C07D409/10
CPCC07D333/12C07D333/20C07D333/28C07D409/10
Inventor 翟光喜汪洋
Owner SHANDONG UNIV
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