CN102731437A - Preparation method of 4-piperazine-3-trifluoromethylaniline hydrochloride - Google Patents
Preparation method of 4-piperazine-3-trifluoromethylaniline hydrochloride Download PDFInfo
- Publication number
- CN102731437A CN102731437A CN2012101976996A CN201210197699A CN102731437A CN 102731437 A CN102731437 A CN 102731437A CN 2012101976996 A CN2012101976996 A CN 2012101976996A CN 201210197699 A CN201210197699 A CN 201210197699A CN 102731437 A CN102731437 A CN 102731437A
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- China
- Prior art keywords
- piperazine
- trifluoromethyl
- reaction
- carboxylic acid
- acid tert
- Prior art date
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention discloses a preparation method of 4-piperazine-3-trifluoromethylaniline hydrochloride. The method comprises: taking 4-nitro-2-trifluoromethyl fluorobenzene as the starting raw material, which is combined with butoxycarbonyl piperazine under an alkaline condition, then conducting hydrogenation and removing BOC (butoxycarbonyl) protection, thus obtaining the target compound.
Description
Technical field
The synthesis technology that the present invention relates to a kind of 4-piperazine-3-trifluoromethylbenzene amine hydrochlorate improves, and belongs to the medicine bioengineering chemical technology field.Also relate to some midbody that obtains through this method.
Background technology
4-piperazine-3-trifluoromethylbenzene amine hydrochlorate is a white solid, is a kind of important biology,drug and chemical industry midbody.
The preparation of 4-piperazine-3-trifluoromethylbenzene amine hydrochlorate is to be starting raw material with 4-nitro-2-trifluoromethyl-fluorobenzene, and alkaline condition combines with tert-butoxycarbonyl-piperazine down, through over hydrogenation, take off BOC and protect, obtains target compound.
Summary of the invention
The present invention mainly improves former operational path, makes per step operation controlled easy to operate, is beneficial to amplify to produce, and improves yield.
The present invention provides formula (4) compound
.
The present invention also provides by formula (3) compound
Ammonification prepares the method for formula (4) compound
This method is to take off BOC by 4-(4-amino-2-trifluoromethyl)-piperazine-1-carboxylic acid tert-butyl ester, and reaction solvent includes but not limited to methyl alcohol, ethanol, ether, ETHYLE ACETATE, acetone, methylene dichloride, chloroform and dioxane, ethyl acetate; Temperature of reaction-5 ~ room temperature is about preferred 0 degree; 1 ~ 8 hour reaction times, preferred 1 ~ 2 hour.
The present invention provides by formula (2) compound
The method for preparing formula (3) compound
With 4-(4-nitro-2-trifluoromethyl)-piperazine-1-carboxylic acid tert-butyl ester is catalyzer hydrogenation with palladium carbon, reaction solvent is methyl alcohol, ethanol, water, ETHYLE ACETATE, THF, methylene dichloride and chloroform, particular methanol; Hydrogen pressure 1 normal atmosphere ~ 60 normal atmosphere, preferred 10 ~ 20 normal atmosphere temperature of reaction, 20 ~ 100 degree, preferred 50 ~ 60 degree; 1 ~ 24 hour reaction times, preferred 8 ~ 12 hours.
The present invention provides by formula (1) compound
The method for preparing formula (2) compound
4-nitro-2-trifluoromethyl-fluorobenzene and tert-butoxycarbonyl-piperazine reaction, reaction solvent includes but not limited to methyl alcohol, ethanol, water, methylene dichloride, chloroform, N, dinethylformamide and DMAC N,N, preferred N, dinethylformamide; Used alkali includes but not limited to sodium hydrogencarbonate, yellow soda ash, salt of wormwood, sodium hydroxide, Pottasium Hydroxide, quadrol, triethylamine and 4-Dimethylamino pyridine, preferred salt of wormwood; Temperature of reaction 0 ~ 120 degree, preferred room temperature; 2 ~ 16 hours reaction times, preferred about 4 hours.
Embodiment
Embodiment 1
100 gram 4-nitro-2-trifluoromethyl-fluorobenzenes are dissolved in 500 milliliters of N, in the dinethylformamide, add 132 gram salt of wormwood and 100 gram tert-butoxycarbonyl-piperazines; 4 hours afterreactions of stirring at room finish, and pour reaction solution in the water into dichloromethane extraction; Anhydrous sodium sulfate drying; Concentrate, separate out solid, filter and obtain 134 gram 4-(4-nitro-2-trifluoromethyl)-piperazine-1-carboxylic acid tert-butyl esters.
Embodiment 2
Getting 50 gram 4-(4-nitro-2-trifluoromethyl)-piperazine-1-carboxylic acid tert-butyl esters is dissolved in 400 ml methanol; Add 3 grams, 10% palladium carbon, in 10 ~ 20 normal atmosphere hydrogen, 50 ~ 60 degree stirred overnight; Be cooled to room temperature; Filter, concentrate, obtain 35 gram 4-(4-amino-2-trifluoromethyl)-piperazine-1-carboxylic acid tert-butyl esters.
Embodiment 3
35 gram 4-(4-amino-2-trifluoromethyl)-piperazine-1-carboxylic acid tert-butyl esters are dissolved in 200 milliliters of ETHYLE ACETATE; Be cooled to about 0 degree, feed excess chlorination hydrogen, insulated and stirred 1 ~ 2 hour; Filter, obtain white solid 20 gram 4-piperazine-3-trifluoromethylbenzene amine hydrochlorates.
Claims (4)
1. the preparation method of 4-piperazine-3-trifluoromethylbenzene amine hydrochlorate is dissolved in N to raw material 4-nitro-2-trifluoromethyl-fluorobenzene, in the dinethylformamide; Add salt of wormwood and tert-butoxycarbonyl-piperazine, stirring at room to reaction finishes, and pours reaction solution in the water into; Extraction, dry concentrating separated out solid; Filtration obtains 4-(4-nitro-2-trifluoromethyl)-piperazine-1-carboxylic acid tert-butyl ester, with 4-(4-nitro-2-trifluoromethyl)-piperazine-1-carboxylic acid tert-butyl ester is catalyzer hydrogenation with palladium carbon, obtains 4-(4-amino-2-trifluoromethyl)-piperazine-1-carboxylic acid tert-butyl ester; 4-(4-amino-2-trifluoromethyl)-piperazine-1-carboxylic acid tert-butyl ester is dissolved in ETHYLE ACETATE, and the ice bath cooling feeds hydrogen chloride gas to saturated; Stirred overnight at room temperature is filtered, and obtains target compound 4-piperazine-3-trifluoromethylbenzene amine hydrochlorate.
2. the preparation method of 4-piperazine-3-trifluoromethylbenzene amine hydrochlorate according to claim 1; It is characterized in that: 4-nitro-2-trifluoromethyl-fluorobenzene and tert-butoxycarbonyl-piperazine reaction; Reaction solvent includes but not limited to methyl alcohol, ethanol, water, methylene dichloride, chloroform, N; Dinethylformamide and DMAC N,N, used alkali include but not limited to sodium hydrogencarbonate, yellow soda ash, salt of wormwood, sodium hydroxide, Pottasium Hydroxide, quadrol, triethylamine and 4-Dimethylamino pyridine; Temperature of reaction 0 ~ 120 degree, 2 ~ 16 hours reaction times.
3. the preparation method of 4-piperazine-3-trifluoromethylbenzene amine hydrochlorate according to claim 1; It is characterized in that: with 4-(4-nitro-2-trifluoromethyl)-piperazine-1-carboxylic acid tert-butyl ester is catalyzer hydrogenation with palladium carbon; Reaction solvent is methyl alcohol, ethanol, water, ETHYLE ACETATE, THF, methylene dichloride and chloroform; Hydrogen pressure 1 normal atmosphere ~ 60 normal atmosphere, temperature of reaction 20 ~ 100 degree, 1 ~ 24 hour reaction times.
4. the preparation method of 4-piperazine-3-trifluoromethylbenzene amine hydrochlorate according to claim 1; It is characterized in that: 4-(4-amino-2-trifluoromethyl)-piperazine-1-carboxylic acid tert-butyl ester takes off BOC; Reaction solvent includes but not limited to methyl alcohol, ethanol, ether, ETHYLE ACETATE, acetone, methylene dichloride, chloroform and dioxane; Temperature of reaction-5 ~ room temperature, 1 ~ 8 hour reaction times.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101976996A CN102731437A (en) | 2012-06-15 | 2012-06-15 | Preparation method of 4-piperazine-3-trifluoromethylaniline hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012101976996A CN102731437A (en) | 2012-06-15 | 2012-06-15 | Preparation method of 4-piperazine-3-trifluoromethylaniline hydrochloride |
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|---|---|
| CN102731437A true CN102731437A (en) | 2012-10-17 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2012101976996A Pending CN102731437A (en) | 2012-06-15 | 2012-06-15 | Preparation method of 4-piperazine-3-trifluoromethylaniline hydrochloride |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103467422A (en) * | 2013-09-13 | 2013-12-25 | 陕西步长高新制药有限公司 | Method for preparing vilazodone intermediate 5-piperazinyl-2-acyl substituted benzofuran |
| CN104163788A (en) * | 2014-07-07 | 2014-11-26 | 湖南华腾制药有限公司 | Preparation method of pyridine derivative |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101824009A (en) * | 2010-05-27 | 2010-09-08 | 北京德众万全药物技术开发有限公司 | Simple preparation method for posaconazole and piperazine intermediate thereof |
-
2012
- 2012-06-15 CN CN2012101976996A patent/CN102731437A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101824009A (en) * | 2010-05-27 | 2010-09-08 | 北京德众万全药物技术开发有限公司 | Simple preparation method for posaconazole and piperazine intermediate thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103467422A (en) * | 2013-09-13 | 2013-12-25 | 陕西步长高新制药有限公司 | Method for preparing vilazodone intermediate 5-piperazinyl-2-acyl substituted benzofuran |
| CN104163788A (en) * | 2014-07-07 | 2014-11-26 | 湖南华腾制药有限公司 | Preparation method of pyridine derivative |
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Application publication date: 20121017 |