CN105037253A - Method for purifying compound through ultrasonic crystal precipitation - Google Patents
Method for purifying compound through ultrasonic crystal precipitation Download PDFInfo
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- CN105037253A CN105037253A CN201510278301.5A CN201510278301A CN105037253A CN 105037253 A CN105037253 A CN 105037253A CN 201510278301 A CN201510278301 A CN 201510278301A CN 105037253 A CN105037253 A CN 105037253A
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- organic solvent
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- mixed solution
- ethyl acetate
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/55—Acids; Esters
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F21/00—Dissolving
- B01F21/02—Methods
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
- B01J19/10—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing sonic or ultrasonic vibrations
Abstract
The invention relates to a method for purifying a compound through ultrasonic crystal precipitation. According to the method, after completing an organic synthesis reaction, a dissolved amount of a first organic solvent is added to the obtained crude product, and ultrasonic dissolving is performed; a second organic solvent is added after completely dissolving, and ultrasonic dissolving is performed, wherein the addition amount of the second organic solvent is 1-3 times the volume of the first organic solvent; and after the target compound is precipitated from the solution, suction filtration is performed, and washing is performed with a mixed solution of the first organic solvent and the second organic solvent so as to obtain the high-purity target compound. According to the present invention, the ultrasonic crystal precipitation method is used, such that the byproducts and the pigment generated during the organic synthesis reaction can be removed, the purity of the target product during the organic synthesis is substantially increased, and the high-purity target compound is obtained.
Description
Technical field
The invention belongs to chemical field, relate to the method for purification of compound, particularly relate to a kind of organic synthesis post-treating method, specifically a kind of ultrasonic method of forcing crystallization purification compound.
Background technology
Organic synthesis plays vital effect in organic synthesis field and even whole chemical field, and improve organic synthesis operational path, Optimal reaction conditions is the needs of industry, is the power promoting industrial progress.
In organic synthesis process, particularly number molecular weight is larger, complicated structure, in the synthesis that operational path is long, the building-up reactions of a lot of compound is not the reaction simply carried out completely, generally all generates with various by product, even some chromogenesis.This directly affects next step reaction of operational path, and badly influences the progress even continuity of operational path of operational path, and makes troubles for the discriminating of important intermediate.
Be generally carry out purification compound by the method for mistake post, this method not only takes time and effort, and is unfavorable for suitability for industrialized production in the past.
Summary of the invention
For above-mentioned technical problem of the prior art, the invention provides a kind of ultrasonic method of forcing crystallization purification compound, the described this ultrasonic method of crystallization purification compound of forcing solves the Methods For Purification organic compound passing through post of the prior art, take time and effort, and the technical problem that purity is not high.
A kind of ultrasonic method of forcing crystallization purification compound of the present invention, the first organic solvent adding meltage in crude product after organic synthesis carries out ultrasonic wave dissolving, add the second organic solvent again after dissolving completely and carry out ultrasonic wave dissolving, the add-on of the second organic solvent is 1 ~ 3 times of the first organic solvent volume, after target compound is separated out from solution, suction filtration, then adopts the mixed solution of the first organic solvent and the second organic solvent to wash, obtains highly purified target compound.
Further, the first described organic solvent is ethyl acetate, methylene dichloride, tetrahydrofuran (THF), toluene, acetone, acetonitrile, methyl alcohol and alcohols equal solvent.
Further, the second described organic solvent is sherwood oil, ethyl acetate, toluene, normal hexane and alkanes equal solvent.
Further, in the mixed solution of the first organic solvent and the second organic solvent, the first described organic solvent and the volume ratio of the second organic solvent are 1 ~ 3:1 ~ 3.
Further, the first described organic solvent and the mixed solution of the second organic solvent are the mixed solution of methylene dichloride and ethyl acetate, in described mixed solution, and methylene dichloride: the volume ratio of ethyl acetate is 1:3.
The present invention adopts the ultrasonic method of crystalline substance of forcing to the compound of purifying in organic synthesis, need not cross pillar, just can remove impurity and pigment, obtain highly purified target compound.
The present invention compares with prior art, and its technical progress is significant.Method of the present invention have employed ultrasonic method of forcing crystalline substance, can remove some by products and pigment of generating in organic synthesis, increase substantially the purity of target product in organic synthesis, obtained highly purified target compound.Operation is simple and feasible for the inventive method, consuming time short, can be applicable to suitability for industrialized production.
Simultaneously method of the present invention is that next step reaction of synthesis route provides huge convenience, for the further optimization of operational path is provided convenience, for the detection of organic synthesis process intermediates and mensuration are provided convenience.
Embodiment
Below by example, the present invention is set forth, but do not limit the present invention.
Agents useful for same of the present invention, solvent are commercially available AR, CP level.
The present invention is raw materials used is the intermediate synthesized in oneself operational path.
The present invention's Rotary Evaporators used is the multiplex vacuum pump of SHZ-D (III) circulating water type, and Shanghai Road capital Instrument Ltd. produces.
Invent the ultrasonic cleaning instrument that ultrasonic apparatus used is sy-7200D, Shanghai sound source ultrasonic instrument equipment company produces.
The present invention's high performance liquid chromatograph used is P230 II high performance liquid chromatograph, and Dalian Yilite Analytical Instrument Co., Ltd produces.
Embodiment 1
This example dabigatran etcxilate synthesis technique intermediate 3-[(3-amino-4-methylamino benzoyl) (pyridine-2-base)-amino] ethyl propionate synthesize example, described building-up reactions equation is as follows:
The synthesis concrete steps of above-mentioned reaction and ultrasonicly force brilliant post-treating method as follows:
(1) take A5.0g in 250ml round-bottomed flask, add 10ml water and 10ml acetate dissolution, stir 2-5 minute;
(2) add 3.0g zinc powder, stirred at ambient temperature reacts 1 hour;
(3) react complete, suction filtration, filtrate dichloromethane extraction, concentrated methylene dichloride phase, obtain reddish-brown oily matter B (impure and pigment), purity is 87.5%.
(4) adding about 1-3ml methylene dichloride, under ultrasonic, force it just to dissolve, then add about 3-5ml ethyl acetate wherein, continuing ultrasonic to separating out solid;
(5) suction filtration, the methylene dichloride with a small amount of: the mixed solvent washing leaching cake of ethyl acetate=1:3, can obtain compound as white solid B.
Above-mentionedly obtain white solid B3.4g, productive rate 81.3%, measure through HPLC, purity is 99.8%.
Embodiment 2
The synthesis of this example dabigatran etcxilate synthesis technique intermediate 3-[(3-amino-4-methylamino benzoyl) (pyridine-2-base)-amino] ethyl propionate, described building-up reactions equation is as follows:
The synthesis concrete steps of above-mentioned reaction are as follows:
(1) take A20g in 500ml round-bottomed flask, add 50ml water and 50ml acetate dissolution, stir 2-5 minute;
(2) add 13g zinc powder, stirred at ambient temperature reacts 1 hour;
(3) react complete, suction filtration, filtrate dichloromethane extraction, concentrated methylene dichloride phase, obtain reddish-brown oily matter B (impure and pigment), purity is 86.7%.
(4) adding about 3-5ml methylene dichloride, under ultrasonic, force it just to dissolve, then add about 5-7ml ethyl acetate wherein, continuing ultrasonic to separating out solid;
(5) suction filtration, the methylene dichloride with a small amount of: the mixed solvent washing leaching cake of ethyl acetate=1:3, can obtain compound as white solid B.
Above-mentionedly obtain white solid B13.4g, productive rate 80.1%, measure through HPLC, purity is 99.6%.
Claims (5)
1. a ultrasonic method of forcing crystallization purification compound, it is characterized in that: the first organic solvent adding meltage in the crude product after organic synthesis carries out ultrasonic wave dissolving, add the second organic solvent again after dissolving completely and carry out ultrasonic wave dissolving, the add-on of the second organic solvent is 1 ~ 3 times of the first organic solvent volume, after target compound is separated out from solution, suction filtration, then adopt the mixed solution of the first organic solvent and the second organic solvent to wash, obtain highly purified target compound.
2. a kind of ultrasonic method of forcing crystallization purification compound according to claim 1, is characterized in that: the first described organic solvent is ethyl acetate, methylene dichloride, tetrahydrofuran (THF), toluene, acetone, acetonitrile, methyl alcohol or alcoholic solvent.
3. a kind of ultrasonic method of forcing crystallization purification compound according to claim 1, is characterized in that: the second described organic solvent is sherwood oil, ethyl acetate, toluene, normal hexane, alkane solvents.
4. a kind of ultrasonic method of forcing crystallization purification compound according to claim 1, is characterized in that: in the mixed solution of the first organic solvent and the second organic solvent, the first described organic solvent and the volume ratio of the second organic solvent are 1 ~ 3:1 ~ 3.
5. a kind of ultrasonic method of forcing crystallization purification compound according to claim 1, it is characterized in that: the first described organic solvent and the mixed solution of the second organic solvent are the mixed solution of methylene dichloride and ethyl acetate, in described mixed solution, methylene dichloride: the volume ratio of ethyl acetate is 1:3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201510278301.5A CN105037253A (en) | 2015-05-27 | 2015-05-27 | Method for purifying compound through ultrasonic crystal precipitation |
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| CN201510278301.5A CN105037253A (en) | 2015-05-27 | 2015-05-27 | Method for purifying compound through ultrasonic crystal precipitation |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107417627A (en) * | 2017-05-12 | 2017-12-01 | 上海开荣化工科技有限公司 | The method of purification of Fluoxastrobin |
| CN110003180A (en) * | 2019-04-17 | 2019-07-12 | 上海大学 | Pyrroles-pyridine-pyrrole class compound post-processing purification process |
| CN111562259A (en) * | 2020-07-03 | 2020-08-21 | 江西省农业科学院农产品质量安全与标准研究所 | Method for preparing copper (II) ion visible probe and application thereof |
Citations (6)
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|---|---|---|---|---|
| CN1324226A (en) * | 1998-08-21 | 2001-11-28 | 努利·E·哈其姆 | No-spill drinking cup apparatus |
| CN101636223A (en) * | 2007-03-19 | 2010-01-27 | 普罗索尼克斯有限公司 | The method for preparing crystal |
| US20100076201A1 (en) * | 2008-09-19 | 2010-03-25 | Semiconductor Energy Laboratory Co., Ltd. | Carbazole Derivative and Method for Producing the Same |
| WO2014020555A2 (en) * | 2012-08-01 | 2014-02-06 | Alembic Pharmaceuticals Limited | An improved process for the preparation of dabigatran etexilate mesylate |
| CN103694166A (en) * | 2013-12-24 | 2014-04-02 | 上海应用技术学院 | Preparation method of 3-[(3-amine-4-methylamino-benzoyl)(pyridin-2-yl)amine]ethyl propionate |
| CN104926579A (en) * | 2015-05-27 | 2015-09-23 | 上海应用技术学院 | Method for changing crystal form of compound in organic synthesis reaction |
-
2015
- 2015-05-27 CN CN201510278301.5A patent/CN105037253A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1324226A (en) * | 1998-08-21 | 2001-11-28 | 努利·E·哈其姆 | No-spill drinking cup apparatus |
| CN101636223A (en) * | 2007-03-19 | 2010-01-27 | 普罗索尼克斯有限公司 | The method for preparing crystal |
| US20100076201A1 (en) * | 2008-09-19 | 2010-03-25 | Semiconductor Energy Laboratory Co., Ltd. | Carbazole Derivative and Method for Producing the Same |
| WO2014020555A2 (en) * | 2012-08-01 | 2014-02-06 | Alembic Pharmaceuticals Limited | An improved process for the preparation of dabigatran etexilate mesylate |
| CN103694166A (en) * | 2013-12-24 | 2014-04-02 | 上海应用技术学院 | Preparation method of 3-[(3-amine-4-methylamino-benzoyl)(pyridin-2-yl)amine]ethyl propionate |
| CN104926579A (en) * | 2015-05-27 | 2015-09-23 | 上海应用技术学院 | Method for changing crystal form of compound in organic synthesis reaction |
Non-Patent Citations (1)
| Title |
|---|
| 程青芳等: "甲磺酸达比加群酯的合成", 《中国新药杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107417627A (en) * | 2017-05-12 | 2017-12-01 | 上海开荣化工科技有限公司 | The method of purification of Fluoxastrobin |
| CN110003180A (en) * | 2019-04-17 | 2019-07-12 | 上海大学 | Pyrroles-pyridine-pyrrole class compound post-processing purification process |
| CN111562259A (en) * | 2020-07-03 | 2020-08-21 | 江西省农业科学院农产品质量安全与标准研究所 | Method for preparing copper (II) ion visible probe and application thereof |
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