CN102952095A - Synthetic method of 2-carboxylic acid ethyl ester-5-brooethyl thiazole - Google Patents
Synthetic method of 2-carboxylic acid ethyl ester-5-brooethyl thiazole Download PDFInfo
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- CN102952095A CN102952095A CN2012103995864A CN201210399586A CN102952095A CN 102952095 A CN102952095 A CN 102952095A CN 2012103995864 A CN2012103995864 A CN 2012103995864A CN 201210399586 A CN201210399586 A CN 201210399586A CN 102952095 A CN102952095 A CN 102952095A
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- carboxylic acid
- thiazole
- ethyl ester
- brooethyl
- synthetic method
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Abstract
The invention discloses a synthetic method of 2-carboxylic acid ethyl ester-5-brooethyl thiazole, wherein the method comprises: utilizing easily obtained 1,3-dichloroacetone and ethyl thiooxamate as raw materials to synthesize 2-carboxylic acid ethyl ester-5-chloromethyl thiazole, and performing an exchange reaction on a halogen to obtain the 2-carboxylic acid ethyl ester-5-brooethyl thiazole.
Description
Technical field
The present invention relates to the synthesis technique of a kind of 2-carboxylic acid, ethyl ester-5-brooethyl thiazole, belong to medicine, chemical technology field.
Background technology
2-carboxylic acid, ethyl ester-5-brooethyl thiazole is a kind of water white transparency needle-like crystal, is the important intermediate raw materials of many medicine intermediates.
Summary of the invention
The present invention is take the 1,3-DCA that is easy to get and sulfo-ethyl oxamide as the synthetic 2-carboxylic acid, ethyl ester of raw material-5-5-chloromethyl thiazole, and then the permutoid reaction by halogen is namely got 2-carboxylic acid, ethyl ester-5-brooethyl thiazole.
The synthetic method of 2-carboxylic acid, ethyl ester of the present invention-5-brooethyl thiazole, 1, the 3-Dichloro acetone is dissolved in the ethanol, add the sulfo-ethyl oxamide, reflux is spent the night, behind the cool to room temperature, direct silica gel column chromatography after concentrated the doing, with the concentrated water white transparency needle-like crystal 2-carboxylic acid, ethyl ester-5-5-chloromethyl thiazole that obtains behind the methylene dichloride wash-out, this crystal is dissolved in the acetone, is cooled to add lithiumbromide behind the zero degree in batches, stirs to add water after 48 hours, the crystallization of the dry inspissated oil ether of dichloromethane extraction ether obtains 2-carboxylic acid, ethyl ester-5-brooethyl thiazole, and two step total recoverys are more than 60%.
Above-mentioned with 1,3-DCA, sulfo-ethyl oxamide and lithiumbromide etc. are as follows for chemical reaction and the reaction formula of the synthetic 2-carboxylic acid, ethyl ester of raw material-5-brooethyl thiazole:
(1) 1,3-DCA is dissolved in the ethanol, and the reaction equation of closing ring with the sulfo-ethyl oxamide is:
(2) reaction equation of 2-carboxylic acid, ethyl ester-5-5-chloromethyl thiazole and lithiumbromide generation halogen exchange is:
Embodiment
Embodiment:
1,3-Dichloro acetone (6.35g, 0.050 mole) and sulfo-ethyl oxamide (6.65g, 0.050 mole) join in the ethanol (75 milliliters), reflux stirred 16 hours, behind the cool to room temperature, and direct silica gel column chromatography after concentrated the doing, with the concentrated water white transparency needle-like crystal 2-carboxylic acid, ethyl ester-5-5-chloromethyl thiazole (5.5g, 65% yield) that obtains behind the methylene dichloride wash-out.
2-carboxylic acid, ethyl ester obtained in the previous step-5-5-chloromethyl thiazole (2.7 grams, 13.2 mmole) be dissolved in the acetone (100 milliliters), add lithiumbromide (10 equivalent) under the ice-water bath cooling and stirring in batches, add stirring at room and add water after 48 hours, the crystallization of the dry inspissated oil ether of dichloromethane extraction ether obtains 2-carboxylic acid, ethyl ester-5-brooethyl thiazole (3g, yield 95%).
Claims (4)
1. the present invention is take the 1,3-DCA that is easy to get and sulfo-ethyl oxamide as the synthetic 2-carboxylic acid, ethyl ester of raw material-5-5-chloromethyl thiazole, and then the permutoid reaction by halogen is namely got 2-carboxylic acid, ethyl ester-5-brooethyl thiazole.
2. the synthetic method of 2-carboxylic acid, ethyl ester-5-brooethyl thiazole as claimed in claim, it is characterized in that: described initial feed refers to that 1,3-DCA and sulfo-ethyl oxamide are raw material.
3. the synthetic method the first step of above-mentioned 2-carboxylic acid, ethyl ester-5-brooethyl thiazole is synthesized 2-carboxylic acid, ethyl ester-5-5-chloromethyl thiazole, and it is characterized in that: solvent is alcohols, preferred alcohol; Temperature is 0-100 ° of C, the boiling point of preferred alcohol.
4. the synthetic method second step of above-mentioned 2-carboxylic acid, ethyl ester-5-brooethyl thiazole synthesizes 2-carboxylic acid, ethyl ester-5-brooethyl thiazole, and it is characterized in that: reagent is acetone, and halogen exchange reagent is lithiumbromide, Potassium Bromide, Sodium Bromide etc., preferred lithiumbromide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012103995864A CN102952095A (en) | 2012-10-19 | 2012-10-19 | Synthetic method of 2-carboxylic acid ethyl ester-5-brooethyl thiazole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2012103995864A CN102952095A (en) | 2012-10-19 | 2012-10-19 | Synthetic method of 2-carboxylic acid ethyl ester-5-brooethyl thiazole |
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| CN102952095A true CN102952095A (en) | 2013-03-06 |
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| CN2012103995864A Pending CN102952095A (en) | 2012-10-19 | 2012-10-19 | Synthetic method of 2-carboxylic acid ethyl ester-5-brooethyl thiazole |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102348708A (en) * | 2009-03-11 | 2012-02-08 | 奥克兰联合服务有限公司 | Prodrug forms of kinase inhibitors and their use in therapy |
| TW201211053A (en) * | 2010-05-10 | 2012-03-16 | Nissan Chemical Ind Ltd | Spiro compound and drug for activating adiponectin receptor |
| CN102596910A (en) * | 2009-10-27 | 2012-07-18 | 奥赖恩公司 | Androgen receptor modulating compounds |
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2012
- 2012-10-19 CN CN2012103995864A patent/CN102952095A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102348708A (en) * | 2009-03-11 | 2012-02-08 | 奥克兰联合服务有限公司 | Prodrug forms of kinase inhibitors and their use in therapy |
| CN102596910A (en) * | 2009-10-27 | 2012-07-18 | 奥赖恩公司 | Androgen receptor modulating compounds |
| TW201211053A (en) * | 2010-05-10 | 2012-03-16 | Nissan Chemical Ind Ltd | Spiro compound and drug for activating adiponectin receptor |
Non-Patent Citations (1)
| Title |
|---|
| WANG J L ET AL: "Structure based design of novel irreversible FAAH inhibitors", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
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| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20130306 |