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

Preparation method of silodosin intermediate

A technology of silodosin and intermediates, which is applied in the field of pharmaceutical chemical synthesis, can solve the problems of difficulty in realizing industrialized production, expensive raw materials, and many side reactions in the system, and achieves broad prospects and industrial application value, and the conditions are uniform and controllable. , easy to operate and simple effect

Active Publication Date: 2019-03-26
ANHUI QINGYUN PHARMA & CHEM
View PDF7 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] This route looks perfect, very novel, and the steps are short. However, due to the selectivity problem of the reaction, there are many side reactions in the system, and it is difficult to achieve a good separation. After several attempts, the ideal result was not obtained.
Make this route difficult to realize industrial production
[0014] In summary, the synthesis of silodosin intermediate [2-(2,2,2-trifluoroethoxy) phenoxy] ethyl methanesulfonate may be difficult to preserve because of expensive raw materials and poor stability , the reagents used in the reaction are highly toxic; or because the yield is low, a dangerous and difficult-to-control reaction is used; or because the reaction selectivity is poor and the product purity is poor, it is difficult to separate and purify

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 silodosin intermediate
  • Preparation method of silodosin intermediate
  • Preparation method of silodosin intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] A kind of preparation method of silodosin intermediate proposed by the present invention, the steps are as follows:

[0045] Synthesis of S1, 2-(2-hydroxyethoxy)benzaldehyde (formula Ⅲ)

[0046] In a 2000mL four-necked flask equipped with mechanical stirring, 200g (1.64mol, 1.0eq) of salicylaldehyde, 145g (1.64mol, 1.0eq) of ethylene carbonate, and 535g (1.64mol, 1.0eq) of cesium carbonate were added successively to participate in the reaction. ), dimethyl sulfoxide 600mL, N-methylpyrrolidone 600mL, under the protection of nitrogen, the temperature was raised to 130°C, and the reaction was incubated for 10 hours. After the sample HPLC raw materials were completely converted, the reaction system was cooled to room temperature and filtered. The filtrate was poured into 1000 mL of ice water, extracted with 500 mL*3 of ethyl acetate, the organic phases were combined, and dried over anhydrous sodium sulfate to obtain 200 g of light yellow oil with a yield of 73.3% and a puri...

Embodiment 2

[0054] A kind of preparation method of silodosin intermediate proposed by the present invention, the steps are as follows:

[0055] Synthesis of S1, 2-(2-hydroxyethoxy)benzaldehyde (formula Ⅲ)

[0056] In a 2000mL four-necked flask equipped with mechanical stirring, 200g (1.64mol, 1.0eq) of salicylaldehyde, 217g (2.46mol, 1.5eq) of ethylene carbonate, and 679g (4.92mol, 3.0eq) of potassium carbonate were added successively to participate in the reaction. ), N,N-dimethylacetamide 1000mL, heated up to 110°C under the protection of nitrogen, kept the reaction for 7 hours, and the raw materials were sampled by HPLC for complete conversion, the reaction system was cooled to room temperature, and filtered. The filtrate was poured into 1000 mL of ice water, extracted with 500 mL*3 of ethyl acetate, the organic phases were combined, and dried over anhydrous sodium sulfate to obtain 216 g of light yellow oil with a yield of 79.1% and a purity of 98.0%.

[0057] Synthesis of S2, 2-(2-h...

Embodiment 3

[0064] A kind of preparation method of silodosin intermediate proposed by the present invention, the steps are as follows:

[0065] Synthesis of S1, 2-(2-hydroxyethoxy)benzaldehyde (formula Ⅲ)

[0066] In a 2000mL four-necked flask equipped with mechanical stirring, 200g (1.64mol, 1.0eq) of salicylaldehyde, 188g (2.13mol, 1.3eq) of ethylene carbonate, and 680g (2.46mol, 3.0eq) of potassium carbonate were added successively. ), N,N-dimethylformamide 1000mL, heated up to 120°C under the protection of nitrogen, and kept the temperature for 9 hours to react. After sampling the HPLC raw material conversion was complete, the reaction system was cooled to room temperature and filtered. The filtrate was poured into 1000 mL of ice water, extracted with 500 mL*3 of ethyl acetate, the organic phases were combined, and dried over anhydrous sodium sulfate to obtain 214 g of light yellow oil with a yield of 78.4% and a purity of 98.2%.

[0067] Synthesis of S2, 2-(2-hydroxyethoxy)sodium ph...

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 a silodosin intermediate and relates to the technical field of chemical synthesis of drugs. The preparation method comprises the following steps: subjecting salicyaldehyde and ethylene carbonate to transesterification to obtain 2-(2-hydroxyethoxy)benzaldehyde; then, carrying out a Dakin oxidation reaction to obtain sodium 2-(2-hydroxyethoxy) phenol;then, subjecting sodium 2-(2-hydroxyethoxy) phenol and trifluoroethanol to an etherification reaction to obtain 2-[2-(2,2,2-trifluoroethyoxy)phenoxy]ethyl alcohol; and finally, subjecting 2-[2-(2,2,2-trifluoroethyoxy)phenoxy]ethyl alcohol and methanesulfonyl chloride to an esterfication reaction to obtain the silodosin intermediate 2-[2-(2,2,2-trifluoroethyoxy)phenoxy]ethyl methanesulfonate. The preparation method is novel and short in synthesis route, and a target product can be prepared by only four-step reaction. Both raw materials and reagents used for preparation are cheap, available andenvironment-friendly, all the reaction conditions are mild and controllable, the preparation method is convenient and simple in operation, and the prepared silodosin intermediate is high in purity andyield, suitable for industrial production and wide in prospect and industrial application value.

Description

technical field [0001] The invention relates to the technical field of medicinal chemical synthesis, in particular to a preparation method of a silodosin intermediate. Background technique [0002] Silodosin (silodosin), the chemical name is 2,3-dihydro-1-(3-hydroxypropyl)-5-[(2R)-2-[2-[2-(2,2,2- Trifluoroethoxy)phenoxy]ethylamino]propyl]-1H-indole-7-carboxamide is an α1A receptor antagonist developed by Japanese Kissei Pharmaceutical Company, which was first listed in Japan in May 2006 , in October 2008 approved by the FDA in the United States officially listed, trade name Urief. Silodosin is used clinically to treat symptoms associated with benign prostatic hyperplasia (BPH) or hypertrophy. [0003] [0004] [2-(2,2,2-trifluoroethoxy) phenoxy] ethyl methanesulfonate (1) is an important intermediate of silodosin, currently the synthesis of (1) mainly contains the following routes. [0005] Synthetic route 1: European patent EP600675 has reported a synthetic route of ...

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): C07C303/28C07C309/66
CPCC07C41/01C07C41/26C07C45/64C07C303/28C07C309/66C07C47/575C07C43/23
Inventor 黄欢黄庆国李凯施亚琴
Owner ANHUI QINGYUN PHARMA & CHEM
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