Synthesis methods of firocoxib and firocoxib intermediate

A firocoxib and synthetic method technology, applied in the field of drug synthesis, can solve problems such as not suitable for large-scale industrial production, unfavorable for the environment and occupational health, strong toxicity and corrosiveness, etc. Improved production efficiency and yield, environmentally friendly effect

Active Publication Date: 2018-02-13
CHENGDU EASTON BIOPHARMACEUTICALS CO LTD +1
View PDF2 Cites 14 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Disadvantage 1: Sulfide anisole is used as the starting material, and sulfides generally have an unpleasant smell, and are easy to burn and explode when exposed to open flames or high heat. This substance will pollute the environment, and production in Europe and the United States has great environmental protection pressure
At the same time, in the post-treatment process of this method, it is necessary to pass through a silica gel chromatography column to obtain relati

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 methods of firocoxib and firocoxib intermediate
  • Synthesis methods of firocoxib and firocoxib intermediate
  • Synthesis methods of firocoxib and firocoxib intermediate

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0044] Specifically, the method for synthesizing Ferocoxib intermediate includes the following steps:

[0045] S1: Using p-bromopropiophenone as a starting material, methylating the p-bromopropiophenone and a methylating reagent to obtain the first intermediate A1.

[0046] Specifically, p-bromopropiophenone is dissolved in the first solvent, a strong base and a methylating reagent are added, ethyl acetate and water are added for liquid separation after the reaction is complete, the organic phase is dried over anhydrous sodium sulfate, and the solvent is evaporated under reduced pressure The first intermediate A1 was obtained.

[0047] The embodiment of the present invention uses p-bromopropiophenone as the starting material to generate the first intermediate A1 through the methylation reaction. The methylation reaction is carried out at room temperature under mild reaction conditions and avoids the use of environmentally unfriendly thioethers as starting materials. Starting materia...

Embodiment 1

[0069] Example 1 Preparation of 1-(4-bromophenyl)-2-methylacetone

[0070] This embodiment provides a method for preparing the first intermediate A1, which takes p-bromopropiophenone as a starting material, and performs a methylation reaction between p-bromopropiophenone and a methylating reagent to obtain the first intermediate A1. The preparation steps are as follows:

[0071] Dissolve p-bromopropiophenone (100g, 1eq) in 400mL dimethylformamide at room temperature, add sodium hydroxide (56.3g, 3eq) and methyl iodide (133.3g, 2eq), and stir overnight at room temperature. After the reaction is complete, add 500 mL ethyl acetate and 500 mL water, extract and separate the layers, the organic phase is dried over anhydrous sodium sulfate, and the solvent is evaporated under reduced pressure to obtain the first intermediate A1, namely: 1-(4-bromophenyl)-2- Methyl acetone, (110g, light yellow liquid).

Embodiment 2

[0072] Example 2 Preparation of 1-(4-bromophenyl)-2-methylacetone

[0073] This embodiment provides a method for preparing the first intermediate A1, which takes p-bromopropiophenone as a starting material, and performs a methylation reaction between p-bromopropiophenone and a methylating reagent to obtain the first intermediate A1. The preparation steps are as follows:

[0074] Dissolve p-bromopropiophenone (5.0 g, 1 eq) in 20 mL DMSO at room temperature, and add lithium hydroxide (2.0 g, 3.7 eq). After stirring until the solid is dissolved, methyl iodide (5.0 g, 1.5 eq) is added dropwise, and the mixture is stirred at room temperature overnight. After the reaction is complete, add 30 mL of ethyl acetate and 30 mL of water, extract and separate the layers, dry the organic phase over anhydrous sodium sulfate, and distill off the solvent under reduced pressure to obtain intermediate A1, namely: 1-(4-bromophenyl)-2-methyl Acetone, (5.8g, light yellow liquid).

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 the field of medicine synthesis and provides synthesis methods of firocoxib and a firocoxib intermediate. The synthesis method of the firocoxib intermediate takes 4'-bromopropiophenone as a starting raw material and a condition that thioether which is not environmentally friendly is used as the starting raw material is avoided; the 4'-bromopropiophenone and a methylating reagent are subjected to methylating reaction to obtain a first intermediate; the first intermediate is subjected to sulphination to directly obtain a second intermediate; sulfidation reaction and oxidization reaction are shortened to one-step substitution reaction, so that reaction steps are extremely simplified, the reaction time is shortened and the reaction efficiency is improved. Meanwhile, anNBS (N-Bromosuccinimide) system is also adopted so that the second intermediate is subjected to hydroxylation reaction to directly obtain the firocoxib intermediate, so that the synthesis method is more environmentally friendly and is suitable for large-scale production, and the reaction speed is improved. Furthermore, the synthesis method of the firocoxib comprises the synthesis method of the firocoxib intermediate and the firocoxib can be synthesized by a manner which has more moderate reaction conditions and is more environmentally friendly.

Description

Technical field [0001] The invention relates to the field of drug synthesis, in particular to a method for synthesizing ferocoxib and its intermediates. Background technique [0002] Ferocoxib, namely 3-(cyclopropylmethoxy)-5,5-dimethyl-4-[4-(methylxanthyl)phenyl]-2(5H)-furanone, molecular formula: C 17 H 20 O 5 S. [0003] Ferocoxib is an important non-steroidal anti-inflammatory drug. There are not many reports on the synthesis of Ferocoxib. There are two main methods: [0004] Method one is the synthetic route of ferocoxib reported in patent documents US5981576, US006020343A, WO971645A1. Take anisole as starting material, react with isobutyryl chloride to produce compound A, compound A is hydroxylated to produce compound B, and compound B is oxidized with an oxidant such as (MMPP monoperoxy phthalate) to produce compound C, compound C It reacts with acetoxyacetyl chloride to produce compound D. Compound D is treated with DBU to close the ring to produce compound E, and compound...

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): C07D307/60C07C315/04C07C317/24
CPCC07C45/68C07C315/00C07C315/04C07D307/60C07C317/24C07C49/807C07C45/46
Inventor 王颖李晓迅邓显华卢铁刚刘时奎
Owner CHENGDU EASTON BIOPHARMACEUTICALS CO LTD
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