CN105541723A - Crystallization process of cimetidine crude product - Google Patents
Crystallization process of cimetidine crude product Download PDFInfo
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- CN105541723A CN105541723A CN201510948008.5A CN201510948008A CN105541723A CN 105541723 A CN105541723 A CN 105541723A CN 201510948008 A CN201510948008 A CN 201510948008A CN 105541723 A CN105541723 A CN 105541723A
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- crude product
- cimetidine
- crystallization
- stirring
- cimitidine type
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a crystallization process of cimetidine crude product. The process comprises the following steps: introducing recirculated cooling water into a crystallization tank wall jacket, and controlling the temperature at 0-3 DEG C and the flow rate at 3-4 m/s; subjecting a cimetidine crude product to filter press into a crystallization tank; starting a stirrer for stirring the cimetidine crude product in the crystallization tank at a speed of 50 r/ min; continuing stirring for 20min, and stopping stirring; 30min later, continuing to stir for 20 min, and stopping stirring; repeating the above steps for 3-4 h until no crystal precipitation; and finally, sucking the crystals into a vacuum drier to obtain the cimetidine product. The invention has the following beneficial effects of: (1) increasing the rate of crystallization, and saving energy; (2) improving the production efficiency and output; (3) increasing the bulk density, facilitating packaging, reducing transport and storage volume of products, improving productivity and output of the downstream customers; therefore, the process is more in line with customer demand and production process.
Description
Technical field
The present invention relates to a kind of crystallization processes, be specifically related to a kind of crystallization processes of Cimitidine Type A/AB crude product.
Background technology
Cimitidine Type A/AB, chemical full name is N-methyl-N-[2 [[(5-methyl isophthalic acid H-imidazol-4 yl) methyl] sulfo-] ethyl]-N-dicyanodiamide, is the first-generation H2-receptor antagonist of 20 century 70 listings.Within 1976, develop listing by GlaxoSmithKline PLC company, obtain FDA approval on June 16th, 1977.It is mainly used in the treatment of peptide ulceration, upper gastrointestinal hemorrhage and acute pancreatitis.In recent years, this medicine also opened novel clinical use, had antiandrogen effect and improved immune function of human body.
Production technique both at home and abroad about Cimitidine Type A/AB comprises the following steps substantially: first raw material is through first time condensation and second time condensation, then obtains Cimitidine Type A/AB by amination reaction, and rear Cimitidine Type A/AB crude product carries out decolouring, crystallization, dry, obtains Cimitidine Type A/AB finished product.At present in disclosed technology, most of investigator is devoted to the selection of raw material and the setting of reaction conditions, not about the report of crystallization technique.
Crystallization purification method is the study hotspot of recent domestic, and the advantage such as relative to the purification of a lot of material, it has, and operational condition is easy to control, temperature is low, it is little to invest, it is little to pollute and product purity is high is one of the most effective way of large scale continuous prod.At present, the product bulk density that Cimitidine Type A/AB crude crystalline obtains is lower, is only 0.2g/cm
3left and right, and its output is lower, and general purification rate, about 75%, can not meet the demand of different client.And the Size-dependent of bulk density is in crystal growing process, primarily of two influence factors: the shape of (1) crystal grain; (2) crystal grain distribution.In crystallization processes, stirring is the important factor controlling grain shape and crystal grain distribution, directly can affect the size of product production and bulk density.In prior art, most of Cimitidine Type A/AB crystallisation process is continuously stirring crystallization, and continuously stirring is unfavorable for that crystal is formed, so just cause its bulk density, output all lower.
For problem existing in above-mentioned prior art, study and a kind ofly make the crystallization processes that the bulk density of Cimitidine Type A/AB crystalline product and output are all higher, thus to overcome problem existing in prior art be very necessary.
Summary of the invention
For solving the problems of the technologies described above, the object of the present invention is to provide a kind of crystallization processes of Cimitidine Type A/AB crude product, the product bulk density that this technique obtains all is being improved with output.
To achieve these goals, the present invention realizes by the following technical solutions:
A crystallization processes for Cimitidine Type A/AB crude product, is characterized in that comprising the following steps:
(1) pass into recirculated cooling water to crystallization tank skin chuck, controlling its temperature is 0 DEG C ~ 3 DEG C, and flow velocity is 3m/s ~ 4m/s;
(2) by the press filtration of Cimitidine Type A/AB crude product in crystallizer;
(3) start agitator to stir the Cimitidine Type A/AB crude product in crystallizer, rotating speed is 50r/min; After Keep agitation 20min, stop stirring; After 30min, continue to stir 20min, stop afterwards stirring; Circulation continuous like this is reciprocal, continues 3h ~ 4h altogether, until separate out without crystal;
(4) crystallisate is sucked in vacuum drier and carry out drying and obtain Cimitidine Type A/AB finished product.
Beneficial effect of the present invention is: (1) adds crystallization velocity, has saved the energy; (2) improve production efficiency and output; (3) increase bulk density, easily pack, reduce the transport of product, storage volume, improve production efficiency and the output of downstream client, more meet demand and the production technique of client.
Embodiment
Be clearly and completely described the technical scheme in the embodiment of the present invention below, obviously, described embodiment is only a part of embodiment of the present invention, instead of whole embodiments.Based on the embodiment in the present invention, those of ordinary skill in the art, not making the every other embodiment obtained under creative work prerequisite, belong to the scope of protection of the invention.
Set forth a lot of detail in the following description so that fully understand the present invention, but the present invention can also adopt other to be different from alternate manner described here to implement, those skilled in the art can when without prejudice to doing similar popularization when intension of the present invention, therefore the present invention is by the restriction of following public specific embodiment.
Embodiment 1
A crystallization processes for Cimitidine Type A/AB crude product, is characterized in that comprising the following steps:
(1) pass into recirculated cooling water to crystallization tank skin chuck, controlling its temperature is 0 DEG C, and flow velocity is 3m/s ~ 4m/s;
(2) by Cimitidine Type A/AB crude product 180kg press filtration in crystallizer;
(3) start agitator to stir the Cimitidine Type A/AB crude product in crystallizer, rotating speed is 50r/min; After Keep agitation 20min, stop stirring; After 30min, continue to stir 20min, stop afterwards stirring; Circulation continuous like this is reciprocal, continues 3h altogether;
(4) crystallisate is sucked in vacuum drier and carry out drying and obtain Cimitidine Type A/AB finished product.
After testing, the bulk density of this Cimitidine Type A/AB finished product is 0.38g/cm
3, output is 158kg, and purification rate is 87.8%, and both are all improved largely.
Embodiment 2
A crystallization processes for Cimitidine Type A/AB crude product, is characterized in that comprising the following steps:
(1) pass into recirculated cooling water to crystallization tank skin chuck, controlling its temperature is 3 DEG C, and flow velocity is 3m/s ~ 4m/s;
(2) by Cimitidine Type A/AB crude product 180kg press filtration in crystallizer;
(3) start agitator to stir the Cimitidine Type A/AB crude product in crystallizer, rotating speed is 50r/min; After Keep agitation 20min, stop stirring; After 30min, continue to stir 20min, stop afterwards stirring; Circulation continuous like this is reciprocal, continues 3.5h altogether;
(4) crystallisate is sucked in vacuum drier and carry out drying and obtain Cimitidine Type A/AB finished product.
After testing, the bulk density of this Cimitidine Type A/AB finished product is 0.40g/cm
3, output is 160kg, and purification rate is 88.9%, and both are all improved largely.
Embodiment 3
A crystallization processes for Cimitidine Type A/AB crude product, is characterized in that comprising the following steps:
(1) pass into recirculated cooling water to crystallization tank skin chuck, controlling its temperature is 2 DEG C, and flow velocity is 3m/s ~ 4m/s;
(2) by Cimitidine Type A/AB crude product 180kg press filtration in crystallizer;
(3) start agitator to stir the Cimitidine Type A/AB crude product in crystallizer, rotating speed is 50r/min; After Keep agitation 20min, stop stirring; After 30min, continue to stir 20min, stop afterwards stirring; Circulation continuous like this is reciprocal, continues 4h altogether;
(4) crystallisate is sucked in vacuum drier and carry out drying and obtain Cimitidine Type A/AB finished product.
After testing, the bulk density of this Cimitidine Type A/AB finished product is 0.42g/cm
3, output is 164kg, and purification rate is 91.1%, and both are all improved largely.
Claims (1)
1. a crystallization processes for Cimitidine Type A/AB crude product, is characterized in that comprising the following steps:
(1) pass into recirculated cooling water to crystallization tank skin chuck, controlling its temperature is 0 DEG C ~ 3 DEG C, and flow velocity is 3m/s ~ 4m/s;
(2) by the press filtration of Cimitidine Type A/AB crude product in crystallizer;
(3) start agitator to stir the Cimitidine Type A/AB crude product in crystallizer, rotating speed is 50r/min; After Keep agitation 20min, stop stirring; After 30min, continue to stir 20min, stop afterwards stirring; Circulation continuous like this is reciprocal, continues 3h ~ 4h altogether, until separate out without crystal;
(4) crystallisate is sucked in vacuum drier and carry out drying and obtain Cimitidine Type A/AB finished product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510948008.5A CN105541723A (en) | 2015-12-17 | 2015-12-17 | Crystallization process of cimetidine crude product |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510948008.5A CN105541723A (en) | 2015-12-17 | 2015-12-17 | Crystallization process of cimetidine crude product |
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| CN105541723A true CN105541723A (en) | 2016-05-04 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201510948008.5A Pending CN105541723A (en) | 2015-12-17 | 2015-12-17 | Crystallization process of cimetidine crude product |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4855439A (en) * | 1987-01-23 | 1989-08-08 | Lek | Process for the preparation of cimetidine |
| CN101157656A (en) * | 2007-10-29 | 2008-04-09 | 常州龙城药业有限公司 | Method for producing cimetidine |
| CN101838241A (en) * | 2009-03-17 | 2010-09-22 | 无锡市凯利药业有限公司 | Production method of cimetidine |
| CN104557720A (en) * | 2015-01-21 | 2015-04-29 | 盐城凯利药业有限公司 | Preparation method of cimetidine |
-
2015
- 2015-12-17 CN CN201510948008.5A patent/CN105541723A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4855439A (en) * | 1987-01-23 | 1989-08-08 | Lek | Process for the preparation of cimetidine |
| CN101157656A (en) * | 2007-10-29 | 2008-04-09 | 常州龙城药业有限公司 | Method for producing cimetidine |
| CN101838241A (en) * | 2009-03-17 | 2010-09-22 | 无锡市凯利药业有限公司 | Production method of cimetidine |
| CN104557720A (en) * | 2015-01-21 | 2015-04-29 | 盐城凯利药业有限公司 | Preparation method of cimetidine |
Non-Patent Citations (1)
| Title |
|---|
| 刘毅，等: "西咪替丁的合成工艺", 《医药工业》 * |
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Application publication date: 20160504 |