CN106892856A - A kind of preparation method of gliclazide crude product recrystallization - Google Patents
A kind of preparation method of gliclazide crude product recrystallization Download PDFInfo
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- CN106892856A CN106892856A CN201710065492.6A CN201710065492A CN106892856A CN 106892856 A CN106892856 A CN 106892856A CN 201710065492 A CN201710065492 A CN 201710065492A CN 106892856 A CN106892856 A CN 106892856A
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- gliclazide
- crude product
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- recrystallized
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
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Abstract
The invention discloses the invention discloses the preparation method that a kind of gliclazide crude product is recrystallized, comprise the following steps, 1）Crude product gliclazide is dissolved in quantitative solvent, adds activated carbon to be heated to reflux；2）Insulation, then filters while hot；3）While filtrate is lowered the temperature, the solvent of quantitative low pole is added dropwise to adjust the polarity of system；4）System cooling crystallization, suction filtration just can obtain fine work gliclazide；The present invention has evaded gliclazide and has been degraded in alkalescent solvent ethyl acetate brought risk using neutral flux；The polarity that weak polar solvent changes solvent is added dropwise, gliclazide almost all crystallization can be made, effectively improve product yield, reduces cost；Raw material is easy to get, and process is simple rationally, is produced without waste water；Compared with existing traditional production technology, with obviously economic benefit and environmental benefit, it is easy to industrial production.
Description
Technical field
The invention belongs to field of medicaments, more particularly to the preparation method that a kind of gliclazide crude product is recrystallized.
Background technology
Gliclazide, English name：Gliclazide, molecular formula：C15H21N3O3S, chemical name 1- [hexahydro ring penta (C) pyrroles-
2 (1H)-yls] -3- (4- aminomethyl phenyls) sulfonylurea.Gliclazide belongs to second generation sulfonylurea OHA, has drop blood concurrently
The double action of sugar and improvement coagulation function, can not only improve the metabolism of diabetic, and can improve or delay sugar
The generation of the sick vascular complication of urine.Gliclazide is developed by French SERVEIR companies, is listed in France in 1972, at home
Clinic is widely used in outward, is also the line orally-taken blood sugar reducing of China one as one of the most frequently used medicine for the treatment of type II diabetes at present
Medicine.Its chemical structural formula is as follows：
The method of traditional gliclazide crude product recrystallization is by gliclazide crude product and quantitative ethyl acetate, activated carbon etc.
Rise and be heated to reflux, filter activity charcoal, crystallization of then lowering the temperature, refilter solvent and just can obtain gliclazide fine work while hot, and yield exists
85% or so, compared with refined preceding crude product, impurity number is more, and purity is also decreased for the gliclazide after refining.This is heavy
There is very big defect in method for crystallising, that is, gliclazide has in ethyl acetate and significantly degrades, and ultimately results in
Refined gliclazide fine work out is sometimes high without crude product purity on the contrary, and overall yield is relatively low.
The content of the invention
For the deficiency that above-mentioned traditional method of purification is present, the purpose of the present invention is exactly to be brought to evade ethyl acetate
Risk, there is provided a kind of process is simple rationally, purity and yield is higher, cost is lower, be more easy to the gliclazide of industrialized production
The preparation method of crude product recrystallization.
Technical solution of the invention is：
One aspect of the present invention provides a kind of preparation method of gliclazide crude product recrystallization, comprises the following steps：
1）Crude product gliclazide is dissolved in quantitative solvent, adds activated carbon to be heated to reflux；
2）Insulation, then filters while hot；
3）While filtrate is lowered the temperature, quantitative weak polar solvent is added dropwise to adjust the polarity of system；
4）System cooling crystallization, suction filtration just can obtain fine work gliclazide.
It is further preferred that step 1）Described in dissolving gliclazide solvent be dichloromethane, chloroform, four
One kind in chloromethanes, tetrahydrofuran.
It is further preferred that step 2）Described in soaking time be 0.1-2 hours.
It is further preferred that step 2）Described in soaking time be 0.5-1 hours.
It is further preferred that step 1）Described in dissolving gliclazide solvent consumption for gliclazide quality 4-
12 times.
It is further preferred that step 3）Described in weak polar solvent be the one kind in petroleum ether, n-hexane, normal heptane.
It is further preferred that step 3）Described in weak polar solvent be 5-15 times of gliclazide quality.
It is further preferred that step 4）Described in system cooling crystallization temperature at -5 DEG C -10 DEG C.
The present invention has the advantages that compared with the prior art：
（1）Gliclazide is evaded to be degraded in alkalescent solvent ethyl acetate brought risk, has been suppressed using neutral flux
Its product palliating degradation degree；
（2）The polarity that weak polar solvent changes solvent is added dropwise, gliclazide almost all crystallization can be made, effectively improve product receipts
Rate, reduces production cost；
（3）Raw material is easy to get, and rationally, whole process is produced process is simple without waste water, waste gas.With existing traditional production technology phase
Than the present invention has obviously economic benefit and environmental benefit.
Specific embodiment
In order to make the purpose , technical scheme and advantage of the present invention be clearer, with reference to embodiments, to the present invention
It is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to
Limit the present invention.
Application principle of the invention is further described with reference to specific embodiment.
Embodiment 1
50g gliclazides crude product, 200 g dichloromethane, 3g activated carbons are added in 1000ml four-hole boiling flasks.It is heated to backflow,
Insulation 30 minutes, filters while hot afterwards.Filtrate is lowered the temperature, while being slowly added dropwise the g of petroleum ether 250.System is cooled to -5 after dripping off
DEG C, at this temperature, insulation crystallization 1 hour.System suction filtration, obtains gliclazide fine work 48.8g, yield 97.6% afterwards.Liquid phase
Area normalization content 99.93%, maximum single miscellaneous 0.03%.
Embodiment 2
50g gliclazides crude product, 400g dichloromethane, 3g activated carbons are added in 2000ml four-hole boiling flasks.Backflow is heated to, is protected
Temperature 60 minutes, filters while hot afterwards.Filtrate is lowered the temperature, while being slowly added dropwise n-hexane 500g.System is cooled to 0 DEG C after dripping off,
At this temperature, insulation crystallization 0.5 hour.System suction filtration, obtains gliclazide fine work 48.3g, yield 96.6% afterwards.Liquid phase
Area normalization content 99.95%, maximum single miscellaneous 0.03%.
Embodiment 3
50g gliclazides crude product, 600 g chloroforms, 3g activated carbons are added in 2000ml four-hole boiling flasks.It is heated to backflow,
Insulation 120 minutes, filters while hot afterwards.Filtrate is lowered the temperature, while being slowly added dropwise the g of normal heptane 750.System is cooled to after dripping off
10 DEG C, at this temperature, insulation crystallization 1 hour.System suction filtration, obtains gliclazide fine work 49.1g, yield 98.2% afterwards.Liquid
Phase area normalizing content 99.91%, maximum single miscellaneous 0.05%.
Embodiment 4
50g gliclazides crude product, 400g tetrachloromethanes, 3g activated carbons are added in 2000ml four-hole boiling flasks.Backflow is heated to, is protected
Temperature 6 minutes, filters while hot afterwards.Filtrate is lowered the temperature, while being slowly added dropwise n-hexane 500g.System is cooled to 0 DEG C after dripping off,
At a temperature of this, insulation crystallization 0.5 hour.System suction filtration, obtains gliclazide fine work 48.1g, yield 96.2% afterwards.Liquidus surface
Product normalizing content 99.94%, maximum single miscellaneous 0.03%.
Embodiment 5
50g gliclazides crude product, 600 g tetrahydrofurans, 3g activated carbons are added in 2000ml four-hole boiling flasks.It is heated to backflow,
Insulation 120 minutes, filters while hot afterwards.Filtrate is lowered the temperature, while being slowly added dropwise the g of normal heptane 750.System is cooled to after dripping off
10 DEG C, at this temperature, insulation crystallization 1 hour.System suction filtration, obtains gliclazide fine work 49.3g, yield 98.6% afterwards.Liquid
Phase area normalizing content 99.92%, maximum single miscellaneous 0.05%.
Although above-mentioned be described to specific embodiment of the invention, not to the limitation of invention protection domain,
One of ordinary skill in the art should be understood that on the basis of technical scheme those skilled in the art need not pay
Various modifications or deform still within the scope of the present invention that creative work can be made.
Claims (8)
1. the preparation method that a kind of gliclazide crude product is recrystallized, it is characterised in that comprise the following steps：
1）Crude product gliclazide is dissolved in quantitative solvent, adds activated carbon to be heated to reflux；
2）Insulation, then filters while hot；
3）While filtrate is lowered the temperature, quantitative weak polar solvent is added dropwise to adjust the polarity of system；
4）System cooling crystallization, suction filtration just can obtain fine work gliclazide.
2. the preparation method that gliclazide crude product according to claim 1 is recrystallized, it is characterised in that step 1）Middle institute
The solvent of the dissolving gliclazide stated is the one kind in dichloromethane, chloroform, tetrachloromethane, tetrahydrofuran.
3. the preparation method that gliclazide crude product according to claim 1 is recrystallized, it is characterised in that step 2）Middle institute
The soaking time stated is 0.1-2 hours.
4. the preparation method that gliclazide crude product according to claim 1 is recrystallized, it is characterised in that step 2）Middle institute
The soaking time stated is 0.5-1 hours.
5. the preparation method that gliclazide crude product according to claim 1 and 2 is recrystallized, it is characterised in that step 1）In
The consumption of the dissolving gliclazide solvent is 4-12 times of the quality of gliclazide.
6. the preparation method that gliclazide crude product according to claim 1 is recrystallized, it is characterised in that step 3）Middle institute
The weak polar solvent stated is the one kind in petroleum ether, n-hexane, normal heptane.
7. the preparation method that gliclazide crude product according to claim 1 is recrystallized, it is characterised in that step 3）Middle institute
It is 5-15 times of gliclazide quality to state weak polar solvent.
8. the preparation method that gliclazide crude product according to claim 1 is recrystallized, it is characterised in that step 4）Middle institute
The temperature of the system cooling crystallization stated is at -5 DEG C -10 DEG C.
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| CN201710065492.6A CN106892856A (en) | 2017-02-06 | 2017-02-06 | A kind of preparation method of gliclazide crude product recrystallization |
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| CN201710065492.6A CN106892856A (en) | 2017-02-06 | 2017-02-06 | A kind of preparation method of gliclazide crude product recrystallization |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20110112266A (en) * | 2008-03-21 | 2011-10-12 | 르 라보레또레 쎄르비에르 | Dividable galenical form allowing modified release of the active ingredient |
| CN102584677A (en) * | 2012-02-07 | 2012-07-18 | 安徽金鼎医药有限公司 | Method for preparing gliclazide |
| CN102993080A (en) * | 2011-09-19 | 2013-03-27 | 浙江九洲药业股份有限公司 | Synthetic method of gliclazide |
| CN103508934A (en) * | 2012-06-27 | 2014-01-15 | 威海威太医药技术开发有限公司 | Preparation method of gliclazide |
-
2017
- 2017-02-06 CN CN201710065492.6A patent/CN106892856A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20110112266A (en) * | 2008-03-21 | 2011-10-12 | 르 라보레또레 쎄르비에르 | Dividable galenical form allowing modified release of the active ingredient |
| CN102993080A (en) * | 2011-09-19 | 2013-03-27 | 浙江九洲药业股份有限公司 | Synthetic method of gliclazide |
| CN102584677A (en) * | 2012-02-07 | 2012-07-18 | 安徽金鼎医药有限公司 | Method for preparing gliclazide |
| CN103508934A (en) * | 2012-06-27 | 2014-01-15 | 威海威太医药技术开发有限公司 | Preparation method of gliclazide |
Non-Patent Citations (3)
| Title |
|---|
| 刘小成，等: "格列齐特的合成研究", 《化学与生物工程》 * |
| 胡春: "《有机化学实验》", 31 December 2014 * |
| 赵武群，等: "格列齐特的合成", 《浙江化工》 * |
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Application publication date: 20170627 |