Synthesis method of 4-fluoro-5-isopropyl-2-methoxyphenylboronic acid

A technology of methoxybenzene boronic acid and methoxy cumene is applied in the field of pharmaceutical intermediate synthesis, and can solve the problems of large-scale production of unfavorable products, poor reaction selectivity, long synthesis route and the like

Active Publication Date: 2016-06-15
CANGZHOU PURUI DONGFANG SCI & TECH
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The above method has defects such as long synthetic route, lack of a large number of suppliers in the individu

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 4-fluoro-5-isopropyl-2-methoxyphenylboronic acid
  • Synthesis method of 4-fluoro-5-isopropyl-2-methoxyphenylboronic acid
  • Synthesis method of 4-fluoro-5-isopropyl-2-methoxyphenylboronic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Synthesis of 4-fluoro-5-isopropyl-2-methoxyphenylboronic acid:

[0026]

[0027] The first step: in the reaction flask, add m-fluoroanisole (12.6 grams, 0.1 moles), 30% hydrogen peroxide (6.2 grams, 0.055 moles) and 130 milliliters of ethanol, after stirring evenly, add iodine (13.2 grams , 0.052 moles), dropwise addition is completed, the reaction solution dissolves clear, and the insulation reaction is continued for 2 hours, the detection reaction is complete, and saturated NaHSO is added 3 The reaction was quenched, 80 milliliters of ethyl acetate was layered, the organic layer was washed with saturated sodium chloride, and distilled to dryness to obtain 22.9 grams of 2-fluoro-4-methoxyiodobenzene;

[0028] Step 2: Mix 2-fluoro-4-methoxyiodobenzene (2.9 g, 91 mmol), isopropylboronic acid (8.0 g, 91 mmol), 1M aqueous sodium carbonate (0.14 mol) and 210 mL of DME After adding the reaction flask, nitrogen gas was blown into the page to remove oxygen, and finally 1...

Embodiment 2

[0031] Synthesis of 4-fluoro-5-isopropyl-2-methoxyphenylboronic acid:

[0032]

[0033] The first step: in the reaction flask, add m-fluoroanisole (12.6 grams, 0.1 moles), 30% hydrogen peroxide (6.2 grams, 0.055 moles) and 130 milliliters of ethanol, after stirring evenly, add iodine (13.2 grams , 0.052 moles), dropwise addition is completed, the reaction solution dissolves clear, and the insulation reaction is continued for 2 hours, the detection reaction is complete, and saturated NaHSO is added 3 The reaction was quenched, 80 milliliters of ethyl acetate was layered, the organic layer was washed with saturated sodium chloride, and distilled to dryness to obtain 22.9 grams of 2-fluoro-4-methoxyiodobenzene;

[0034] Step 2: Mix 2-fluoro-4-methoxyiodobenzene (2.9 g, 91 mmol), isopropylboronic acid (8.0 g, 91 mmol), 1M aqueous potassium carbonate (0.14 mol) and 210 mL of DME After adding the reaction flask, nitrogen gas was blown into the page to remove oxygen, and finall...

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 synthesis method of 4-fluoro-5-isopropyl-2-methoxyphenylboronic acid. The method includes: starting from m-fluoroanisole, carrying out reaction with iodine to conduct iodination, then performing catalytic coupling with isopropylboronic acid, finally conducting selective deprotonation/boronation under a large steric hindrance alkali condition, and performing hydrolysis to obtain a product. The method has the advantages of reasonable route design, simple operation and high selectivity, and is suitable for industrial amplification.

Description

technical field [0001] The invention relates to a method for synthesizing 4-fluoro-5-isopropyl-2-methoxyphenylboronic acid, which belongs to the field of synthesis of pharmaceutical intermediates. Background technique [0002] Arteriosclerosis is the main cause of many diseases and deaths, especially in developed countries. Increasing high-density lipoprotein can effectively reduce sudden cerebrovascular diseases. Currently, one of the most effective drugs is Anacetrapib, which is used clinically as a cholesteryl ester transfer protein (CETP) inhibitor. [0003] As an important structural unit of ansertrapib, there are three main synthesis methods of 4-fluoro-5-isopropyl-2-methoxyphenylboronic acid: [0004] Method 1. Starting from 2,4-difluorobromobenzene, S N The Ar reaction selectively yields 2-methoxy-4-fluorobromobenzene (first step), followed by the Friedel-Crafts reaction with an acetyl group to 2-fluoro-4-methoxy-5-bromoacetophenone (second Two steps), followed by...

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): C07F5/02
CPCC07F5/025
Inventor 冷延国田利国于伟东
Owner CANGZHOU PURUI DONGFANG SCI & TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap