CN102796120A - Method for preparing cefaclor - Google Patents
Method for preparing cefaclor Download PDFInfo
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- CN102796120A CN102796120A CN2012103029680A CN201210302968A CN102796120A CN 102796120 A CN102796120 A CN 102796120A CN 2012103029680 A CN2012103029680 A CN 2012103029680A CN 201210302968 A CN201210302968 A CN 201210302968A CN 102796120 A CN102796120 A CN 102796120A
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- cefaclor
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- salt
- cephalosporanic acid
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Abstract
The invention discloses a preparation method for cefaclor, comprising the steps of: forming a salt by 7-amino-3-chlorocephalosporanic acid and a nitrogen-containing organic base, reacting the salt with a mixed anhydride solution obtained from the reaction of phenylglycine salt and pivaloyl chloride in the action of a catalyst through an acylation condensation reaction, adding an acid for hydrolysis and decoloring, filtering, adding the filtrate dropwise in water and simultaneously using a base to adjust the pH to a cefaclor isoelectric point, culturing crystals, filtering, washing and drying to obtain cefaclor. By the above manner, the invention provides the preparation method for the cefaclor. The method is short in process routes. The cefaclor can be obtained directly by a one-step method. The method helps to save process time, also save the cost of raw materials significantly, and improve the quality and the yield of the product. At the same time the product is high in purity and good in color grade, and can be produced in a large scale.
Description
Technical field
The present invention relates to field of medicaments, particularly relate to a kind of preparation method of cefaclor.
Background technology
Cefaclor is a kind of semi-synthetic s-generation oral cephalosporin; Multiple gram-positive microorganism and Gram-negative bacteria all had very strong killing action; Having efficient, wide spectrum and better chemical stability, is one of important drugs of present clinical treatment infectation of bacteria.Cefaclor because of it has wide spectrum, efficient and good clinical safety, has received people's widespread use and highly high praise all the time since nineteen seventies successfully goes on the market.
Generally to adopt 7-amino-3-chloro Cephalosporanic acid be the reaction of raw material and nitrogenous organic base in the preparation of cefaclor traditionally; In the presence of catalyzer, carry out acylation reaction; Add N again, dinethylformamide forms mixture, transforms and just can obtain the cefaclor bulk drug.This method process step is long; Synthetic difficulty is big; The yield of product is low, the look level is bad, thereby causes the production cost of cephalo Lip river gram high, and selling price is very expensive; Limit the widespread use of cefaclor product, particularly in not rich developing country, can not obtain large-scale clinical application.
Summary of the invention
The technical problem that the present invention mainly solves provides a kind of preparation method of cefaclor, and this method operational path is simple, raw materials cost is low.
For solving the problems of the technologies described above, the technical scheme that the present invention adopts is: a kind of preparation method of cefaclor is provided, comprises that step is:
(1) 7-amino-3-chloro Cephalosporanic acid and nitrogenous organic base salify and be dissolved in the organic solvent obtain 7-amino-3-chloro Cephalosporanic acid lysate;
(2) with phenylglycine Deng salt and pivaloyl chloride be material dissolution in organic solvent, reaction obtains mixed acid anhydride solution under the effect of pyridines catalyzer;
(3) 7-amino-3-chloro Cephalosporanic acid lysate and the acidylate condensation reaction under the effect of pyridines catalyzer of mixed acid anhydride solution add acid hydrolysis, and phase-splitting obtains the cefaclor and the sour salifiable aqueous solution;
(4) to cefaclor and sour salifiable aqueous solution decolouring, filter, filtrating drips in the entry and regulates the pH value to the cefaclor iso-electric point with alkali simultaneously, and growing the grain filters, washing, and drying obtains cefaclor.
In preferred embodiment of the present invention, the quality of water described in the step (4) is 1-2 a times of said 7-amino-3-chloro Cephalosporanic acid quality, and said water is purified water.
In preferred embodiment of the present invention, alkali comprises one or more in Pottasium Hydroxide, sodium hydroxide, salt of wormwood, saleratus, yellow soda ash, sodium hydrogencarbonate, triethylamine, the ammoniacal liquor described in the step (4).
In preferred embodiment of the present invention, alkali described in the step (4) is that mass percent is 10% ammoniacal liquor.
In preferred embodiment of the present invention, rearing crystal time is 2 hours described in the step (4).
In preferred embodiment of the present invention, the pH value is adjusted to 4.0-5.0 described in the step (4).
The invention has the beneficial effects as follows: the preparation method of cefaclor of the present invention; This method operational path is brief; Can adopt single stage method directly to obtain cefaclor, also practice thrift the cost of raw materials for production when having practiced thrift the process time greatly, the mass yield of product has been brought up to 1.42-1.45 from traditional 1.33; Product gas purity is high simultaneously, the look level is good, can scale operation.
Embodiment
Set forth in detail in the face of preferred embodiment of the present invention down, thereby protection scope of the present invention is made more explicit defining so that advantage of the present invention and characteristic can be easier to it will be appreciated by those skilled in the art that.
Embodiment:
(1) taking by weighing 50g 7-amino-3-chloro Cephalosporanic acid is dissolved in the 250ml methylene dichloride and adds in the 500ml four-hole reaction flask; Temperature of reaction system is reduced to-10 ℃--5 ℃; Add the 36g tetramethyl guanidine, stir and obtain 7-amino-3-chloro Cephalosporanic acid lysate after 30 minutes;
(2) in 1000ml four-hole reaction flask, add 200ml methylene dichloride and 100ml N; The N-N,N-DIMETHYLACETAMIDE takes by weighing 78g phenylglycine Deng's salt and 0.05g 4-dimethylamino pyridine joins in the mixing solutions, stirs after 10 minutes; Place the four-hole reaction flask liquid nitrogen to make temperature of reaction system reduce to-35 ℃--30 ℃; Drip the 31.8g pivaloyl chloride in the reaction flask, in temperature be-condition of 75-℃--65 ℃ under stirring reaction 1 hour, obtain mixed acid anhydride solution;
(3) the 7-amino that makes step (1)-3-chloro Cephalosporanic acid lysate is added drop-wise in the mixed acid anhydride solution that step (2) makes; Being-50 ℃--40 ℃ in temperature reacted 4 hours down; Follow the tracks of the detection reaction terminal point through HPLC; When 7-amino in the system-3-chloro Cephalosporanic acid content during less than 2mg/ml, reaction finishes, and in system, adds 350g deionized water and 55g concentrated hydrochloric acid; Stir standing demix after 30 minutes, obtaining the upper strata is the cefaclor and the sour salifiable aqueous solution;
(4) add gac in the cefaclor and the sour salifiable aqueous solution and decolour, filter, obtain filtrating, in reaction flask, add the 75g purified water; Dripping filtrating in the water on one side, is 10% ammoniacal liquor Yi Bian drip mass percent, and pH value of solution value to cefaclor iso-electric point drips until crystallization complete until filtrating in the conditioned reaction bottle; Growing the grain 2 hours filters, and washs with purified water; Drying obtains the 72.5g cefaclor, and the mass yield of cephalo Lip river gram is 1.42-1.45.
The preparation method of the cefaclor that the present invention discloses, this method operational path is brief, and the cefaclor that makes and the sour salifiable aqueous solution need be through not adding N; Dinethylformamide forms mixture and obtains the product cefaclor again; Can adopt single stage method directly to obtain cefaclor, also practice thrift the cost of raw materials for production when having practiced thrift the process time greatly, the mass yield of product has been brought up to 1.42-1.45 from traditional 1.33; Product gas purity is high simultaneously, the look level is good, can scale operation.
The above is merely embodiments of the invention; Be not so limit claim of the present invention; Every equivalent structure or equivalent flow process conversion that utilizes specification sheets of the present invention to do, or directly or indirectly be used in other relevant technical fields, all in like manner be included in the scope of patent protection of the present invention.
Claims (6)
1. the preparation method of a cefaclor is characterized in that, comprises that step is:
(1) 7-amino-3-chloro Cephalosporanic acid and nitrogenous organic base salify and be dissolved in the organic solvent obtain 7-amino-3-chloro Cephalosporanic acid lysate;
(2) with phenylglycine Deng salt and pivaloyl chloride be material dissolution in organic solvent, reaction obtains mixed acid anhydride solution under the effect of pyridines catalyzer;
(3) 7-amino-3-chloro Cephalosporanic acid lysate and the acidylate condensation reaction under the effect of pyridines catalyzer of mixed acid anhydride solution add acid hydrolysis, and phase-splitting obtains the cefaclor and the sour salifiable aqueous solution;
(4) to cefaclor and sour salifiable aqueous solution decolouring, filter, filtrating drips in the entry and regulates the pH value to the cefaclor iso-electric point with alkali simultaneously, and growing the grain filters, washing, and drying obtains cefaclor.
2. the preparation method of cefaclor according to claim 1 is characterized in that, the quality of water described in the step (4) is 1-2 a times of said 7-amino-3-chloro Cephalosporanic acid quality, and said water is purified water.
3. the preparation method of cefaclor according to claim 1 is characterized in that, alkali comprises one or more in Pottasium Hydroxide, sodium hydroxide, salt of wormwood, saleratus, yellow soda ash, sodium hydrogencarbonate, triethylamine, the ammoniacal liquor described in the step (4).
4. the preparation method of cefaclor according to claim 3 is characterized in that, alkali described in the step (4) is that mass percent is 10% ammoniacal liquor.
5. the preparation method of cefaclor according to claim 1 is characterized in that, rearing crystal time is 2 hours described in the step (4).
6. the preparation method of cefaclor according to claim 1 is characterized in that, the pH value is adjusted to 4.0-5.0 described in the step (4).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012103029680A CN102796120A (en) | 2012-08-24 | 2012-08-24 | Method for preparing cefaclor |
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| CN2012103029680A CN102796120A (en) | 2012-08-24 | 2012-08-24 | Method for preparing cefaclor |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105769873A (en) * | 2016-03-17 | 2016-07-20 | 华北制药河北华民药业有限责任公司 | Cefaclor preparation and preparation method thereof |
| CN106008247A (en) * | 2016-06-30 | 2016-10-12 | 宜兴市前成生物有限公司 | Glutamic acid refinement system |
| CN107827910A (en) * | 2017-11-01 | 2018-03-23 | 江西富祥药业股份有限公司 | Ampicillin impurity I preparation method |
| CN109608477A (en) * | 2018-12-28 | 2019-04-12 | 华北制药股份有限公司 | A kind of synthetic method of cephalosporin |
| CN111057072A (en) * | 2019-12-16 | 2020-04-24 | 广州维奥康药业科技有限公司 | Cefaclor impurity removal method |
| CN111187284A (en) * | 2020-03-10 | 2020-05-22 | 赵俊瑶 | Preparation method of cefaclor |
| CN111440197A (en) * | 2020-04-09 | 2020-07-24 | 辽宁美亚制药有限公司 | Preparation method of ceftriaxone sodium |
| CN112574233A (en) * | 2020-12-30 | 2021-03-30 | 苏州盛达药业有限公司 | Cefaclor bulk drug |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0523585A2 (en) * | 1991-07-15 | 1993-01-20 | BIOCHEMIE Gesellschaft m.b.H. | Improvements in or relating to beta lactam production |
| CN1982315A (en) * | 2005-12-14 | 2007-06-20 | 陈舒明 | Synthesis of cefaclor |
-
2012
- 2012-08-24 CN CN2012103029680A patent/CN102796120A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0523585A2 (en) * | 1991-07-15 | 1993-01-20 | BIOCHEMIE Gesellschaft m.b.H. | Improvements in or relating to beta lactam production |
| CN1982315A (en) * | 2005-12-14 | 2007-06-20 | 陈舒明 | Synthesis of cefaclor |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105769873A (en) * | 2016-03-17 | 2016-07-20 | 华北制药河北华民药业有限责任公司 | Cefaclor preparation and preparation method thereof |
| CN106008247A (en) * | 2016-06-30 | 2016-10-12 | 宜兴市前成生物有限公司 | Glutamic acid refinement system |
| CN107827910A (en) * | 2017-11-01 | 2018-03-23 | 江西富祥药业股份有限公司 | Ampicillin impurity I preparation method |
| CN109608477A (en) * | 2018-12-28 | 2019-04-12 | 华北制药股份有限公司 | A kind of synthetic method of cephalosporin |
| CN111057072A (en) * | 2019-12-16 | 2020-04-24 | 广州维奥康药业科技有限公司 | Cefaclor impurity removal method |
| CN111187284A (en) * | 2020-03-10 | 2020-05-22 | 赵俊瑶 | Preparation method of cefaclor |
| CN111440197A (en) * | 2020-04-09 | 2020-07-24 | 辽宁美亚制药有限公司 | Preparation method of ceftriaxone sodium |
| CN112574233A (en) * | 2020-12-30 | 2021-03-30 | 苏州盛达药业有限公司 | Cefaclor bulk drug |
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Application publication date: 20121128 |