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Method for preparing and purifying Silodosin intermediates

A purification method and compound technology, which is applied in the direction of ether preparation, sulfonate ester preparation, ester reaction preparation of ether, etc., can solve the problems of long route, low yield, lack of yield, etc., and achieve simple reaction operation and high total yield , the effect of high purity

Inactive Publication Date: 2012-01-18
SICHUAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

2-(2,2,2-trifluoroethoxy)phenol (Ⅱ); 2-(2,2,2,-trifluoroethoxy)phenoxyethyl methanesulfonate (Ⅰ) is synthesized The key intermediate of silodosin, its synthesis method is reported a lot, but all need column chromatography to purify, lack the high yield, the method that is suitable for industrialized production
[0009] In summary, the current synthesis of silodosin intermediates has a long route and low yield, and needs to be purified by column chromatography, which is not suitable for industrial production

Method used

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  • Method for preparing and purifying Silodosin intermediates

Examples

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Embodiment 1

[0019] Example 1 Synthesis of 2-(2,2,2-trifluoroethoxy)phenol (II)

[0020] 100.0g (0.91mol) of o-diphenol, 112.0g (0.41mol) of p-toluenesulfonic acid-2,2,2-trifluoroethyl ester, 50.8g (0.91mol) of potassium hydroxide, 1.0g (6.7 mmol) and 100ml DMF were mixed, stirred at 100°C for 8 hours, poured the reaction solution into 800ml ice water, adjusted the pH value to about 4 with hydrochloric acid, extracted 3 times with 400ml dichloromethane respectively, combined the dichloromethane layers, and decompressed The dichloromethane was evaporated, the residue was distilled with water steam, the fraction was extracted with dichloromethane, the organic layer was dried over anhydrous sodium sulfate, filtered, and the dichloromethane was evaporated under reduced pressure to obtain 52.0 g of a white solid with a yield of 66%, melting point 50-51°C.

Embodiment 2

[0021] Example 2 Synthesis of 2-(2,2,2,-trifluoroethoxy)phenoxyethyl methanesulfonate (I)

[0022] Mix 100g (0.52mol) of 2-(2,2,2-trifluoroethoxy)phenol, 490g (1.56mol) of ethylene dimesylate, and 100g (0.75mol) of potassium carbonate in 1200ml of acetonitrile, After reflux and stirring for 5 hours, the solvent was evaporated under reduced pressure, and 2500 ml of dichloromethane was added to dissolve the residue, which was washed three times with 500 ml of water respectively. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to evaporate the dichloromethane. The residue was recrystallized with ethyl acetate:petroleum ether (1:50), filtered, and the resulting solid was recrystallized with absolute ethanol, the precipitated solid was discarded, and the filtrate was concentrated, then purified with ethyl acetate:petroleum ether (1:50). 50) Recrystallize, filter, and dry to obtain 85 g of solid, with a yield of 53% and a ...

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Abstract

The invention discloses a method for preparing and purifying Silodosin intermediates namely 2-(2,2,2-tirfluoroethyoxy) phenol and 2-(2,2,2-tirfluoroethyoxy) phenoxy ethyl methanesulfonate. The method comprises the steps of: A. reacting catechol or a salt thereof, 2-halogenated trifluoroethane or 2,2,2-trifluoroethyl sulfonate as raw materials with alkali metal iodide in an aprotic solvent under the action of basic compound to obtain 2-(2,2,2-trifluoroethoxy) phenol (II), and carrying out steam distillation and purification; and B. reacting 2-(2,2,2-trifluoroethoxy) phenol (II) obtained in the step A with ethylene dimethanesulfonate in the aprotic solvent to obtain 2-(2,2,2-trifluoroethoxy) phenoxy ethyl methanesulfonate (I). The method has the advantages that the starting raw materials are inexpensive and easily available, and the production cost is lowered; complicated column chromatography is not used; and the method is suitable for large-scale industrial production.

Description

technical field [0001] The present invention relates to a silodosin intermediate 2-(2,2,2,-trifluoroethoxy)phenoxyethyl methanesulfonate; 2-(2,2,2,-trifluoro Ethoxy) phenoxyethyl methanesulfonate preparation and purification method. Background technique [0002] The structure type of silodosin belongs to phenalkamine compounds. Its chemical name is: (R)-(-)-1-(3-hydroxypropyl)-5-[2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy ]ethylamino]propyl]-7-carbamoylindoline. [0003] [0004] Silodosin has a selective inhibitory effect on the contraction of urethral smooth muscle, and reduces the intraurethral pressure, but has no great effect on blood pressure, and is used for the treatment of benign prostatic hyperplasia. 2-(2,2,2-trifluoroethoxy)phenol (Ⅱ); 2-(2,2,2,-trifluoroethoxy)phenoxyethyl methanesulfonate (Ⅰ) is synthesized The key intermediate of silodosin has many synthetic methods, but all of them need to be purified by column chromatography, which lacks a high yield and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C309/68C07C303/30C07C43/23C07C41/16
Inventor 吴勇海俐李杰李晓岑袁华杰
Owner SICHUAN UNIV
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