CN105130925A - Preparation method of 2-(Z)-(2-aminothiazol-4-yl)-2-acetoxyiminoacetic acid-2-benzothiazolthioester - Google Patents
Preparation method of 2-(Z)-(2-aminothiazol-4-yl)-2-acetoxyiminoacetic acid-2-benzothiazolthioester Download PDFInfo
- Publication number
- CN105130925A CN105130925A CN201510452590.6A CN201510452590A CN105130925A CN 105130925 A CN105130925 A CN 105130925A CN 201510452590 A CN201510452590 A CN 201510452590A CN 105130925 A CN105130925 A CN 105130925A
- Authority
- CN
- China
- Prior art keywords
- reaction
- filter cake
- preparation
- cooled
- cefdinir
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/70—Sulfur atoms
- C07D277/74—Sulfur atoms substituted by carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Cephalosporin Compounds (AREA)
Abstract
The invention provides a preparation method of 2-(Z)-(2-aminothiazol-4-yl)-2-acetoxyiminoacetic acid-2-benzothiazolthioester. The preparation method comprises that 2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetate is put into a reaction bottle with water, the solution in the reaction bottle is heated to a temperature of 30 DEG C, a prepared alkali liquor is dropwisely added into the reaction bottle, the mixed solution is heated to a temperature of 45 DEG C and undergoes a reaction under thermal insulation for 2h, the reaction product is cooled to a room temperature, acetic anhydride is dropwisely added into the reaction product, the prepared alkali liquor is dropwisely added into the mixture to adjust pH to 7, the mixture undergoes a reaction under thermal insulation for 1h, the reaction product is cooled to 0 DEG C, the cooled reaction product is filtered, filter residue is beat and washed by water and acetone so that filter cake is obtained, the filter cake is put into a reaction bottle with acetone, is subjected to heating reflux, is cooled and is filtered, the filter residue is dried by a pump so that filter cake is obtained, the filter cake is put into a reaction bottle with dichloromethane, dibenzothiazyl disulfide is added into the reaction bottle, the mixture is subjected to reflux and then is cooled to a room temperature, triphenyl phosphine and triethylanmine are added into the cooled materials, the mixture undergoes a reaction for 2h, the product is filtered, the filter residue is dried by a pump to obtain filter cake, the filter cake is beat and washed by dichloromethane and then is filtered, and the filter residue is dried by a pump and then is dried to form a desired product. The preparation method has simple processes and good reappearance and improves side chain reaction activity by change of cefdinir side chain groups.
Description
Technical field
The invention belongs to medical synthesis field, relate to the preparation of medicine intermediate, particularly relate to the preparation method of the active new ester of a kind of Cefdinir.
Background technology
Cefdinir is one of important third generation semi-synthetic cephalosporins microbiotic kind, and have sterilizing power strong, has a broad antifungal spectrum, not easily produces the feature of resistance, be widely applied clinically, is one of up-to-date in the market oral cephalosporins medicine.General employing 7-AVCA active ester method synthesis at present obtains, the cynnematin side chain that the more use mercaptobenzothiazole of active ester is modified.In the production of Cefdinir bulk drug, the active new ester of Cefdinir is its important medicine intermediate, and its Product Activity directly affects synthesis yield and the quality of Cefdinir.Several years ago most domestic adopts Cefdinir active ester, and the external active new ester of Cefdinir that substantially adopts, nearest one or two years, the domestic new ester technique of activity that progressively adopts, impelled active new ester development very fast.The structural formula of the active new ester of Cefdinir is:
Summary of the invention
For the problems referred to above, the object of the invention is to provide the preparation method of the active new ester of a kind of Cefdinir, the method have simple to operate, the active new ester of high purity Cefdinir can be prepared.
The present invention solves the problems of the technologies described above adopted technical scheme:
A preparation method for the active new ester of Cefdinir, it is characterized in that, its concrete steps are as follows:
(1) being equipped with in the reaction flask of water by going methylamine thiophene oxime acid esters to put into, being warming up to 30 DEG C, drip the alkali lye prepared, be warming up to 45 DEG C, insulation reaction 2h, be then down to room temperature, drip acetic anhydride, dripping the alkali lye prepared regulates pH to neutral, adds, insulation reaction 1h, 0 DEG C is cooled to after reaction terminates, filter, rinse with water and acetone making beating, obtain filter cake;
(2) be equipped with in the reaction flask of acetone by filter cake input, reflux, backflow terminates, cooling, filter, drain to obtain filter cake, filter cake is dropped into and is equipped with in the reaction flask of methylene dichloride, add dibenzothiazyl disulfide again, heating reflux reaction, be cooled to room temperature, add triphenyl phosphorus and triethylamine, reaction 2h, after reaction terminates, filtration is drained, and filter cake methylene dichloride making beating is rinsed, and final filtration is drained, take out material, carry out drying, obtain target product.
Further, the alkali lye in step (1) is sodium hydroxide solution or potassium hydroxide solution.
Further, in step (1), the massfraction of alkali lye is 30%.
Further, filter cake in step (2): dibenzothiazyl disulfide: triphenyl phosphorus: triethylamine charged material weight is than being 1:1.9:1.5:0.5.
The invention has the advantages that: the preparation method that the invention provides the active new ester of Cefdinir, the method have simple to operate, circulation ratio is strong, the active new ester of the Cefdinir prepared has high-content and highly purified feature, by changing Cefdinir side-chain radical, improve the reactive behavior of side chain.
Embodiment
Embodiment 1
(1) being gone by 30g methylamine thiophene oxime acid esters to put into is equipped with in the reaction flask of water, is warming up to 30 DEG C, drips 30% sodium hydroxide solution prepared, be warming up to 45 DEG C, insulation reaction 2h, be then down to room temperature, drip acetic anhydride, drip 30% sodium hydroxide solution prepared, regulate pH to neutral, add, insulation reaction 1h, is cooled to 0 DEG C after reaction terminates, and filters, rinse with water and acetone making beating, obtain filter cake;
(2) be equipped with in the reaction flask of acetone by filter cake input, reflux, backflow terminates, cooling, filter, drain to obtain filter cake, filter cake is dropped into and is equipped with in the reaction flask of methylene dichloride, add dibenzothiazyl disulfide again, heating reflux reaction, be cooled to room temperature, add triphenyl phosphorus and triethylamine, reaction 2h, after reaction terminates, filtration is drained, and filter cake methylene dichloride making beating is rinsed, and final filtration is drained, take out material, carry out drying, obtain the active new ester of target product Cefdinir.60 DEG C, under 90kPa, vacuum-drying 1.5h, obtains product 34.50g, HPLC testing product content >=98.5%, moisture content≤0.3%.
The above is only preferred embodiment of the present invention, not does any pro forma restriction to technical scheme of the present invention.Every above embodiment is done according to technical spirit of the present invention any simple modification, equivalent variations and modification, all still belong in the scope of technical scheme of the present invention.
Claims (4)
1. a preparation method for the active new ester of Cefdinir, it is characterized in that, its concrete steps are as follows:
(1) being equipped with in the reaction flask of water by going methylamine thiophene oxime acid esters to put into, being warming up to 30 DEG C, drip the alkali lye prepared, be warming up to 45 DEG C, insulation reaction 2h, be then down to room temperature, drip acetic anhydride, dripping the alkali lye prepared regulates pH to neutral, adds, insulation reaction 1h, 0 DEG C is cooled to after reaction terminates, filter, rinse with water and acetone making beating, obtain filter cake;
(2) be equipped with in the reaction flask of acetone by filter cake input, reflux, backflow terminates, cooling, filter, drain to obtain filter cake, filter cake is dropped into and is equipped with in the reaction flask of methylene dichloride, add dibenzothiazyl disulfide again, heating reflux reaction, be cooled to room temperature, add triphenyl phosphorus and triethylamine, reaction 2h, after reaction terminates, filtration is drained, and filter cake methylene dichloride making beating is rinsed, and final filtration is drained, take out material, carry out drying, obtain target product.
2. the preparation method of the active new ester of a kind of Cefdinir according to claim 1, it is characterized in that, the alkali lye in step (1) is sodium hydroxide solution or potassium hydroxide solution.
3. the preparation method of the active new ester of a kind of Cefdinir according to claim 1, it is characterized in that, in step (1), the massfraction of alkali lye is 30%.
4. the preparation method of the active new ester of a kind of Cefdinir according to claim 1, is characterized in that, filter cake in step (2): dibenzothiazyl disulfide: triphenyl phosphorus: triethylamine charged material weight is than being 1:1.9:1.5:0.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510452590.6A CN105130925A (en) | 2015-07-28 | 2015-07-28 | Preparation method of 2-(Z)-(2-aminothiazol-4-yl)-2-acetoxyiminoacetic acid-2-benzothiazolthioester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510452590.6A CN105130925A (en) | 2015-07-28 | 2015-07-28 | Preparation method of 2-(Z)-(2-aminothiazol-4-yl)-2-acetoxyiminoacetic acid-2-benzothiazolthioester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105130925A true CN105130925A (en) | 2015-12-09 |
Family
ID=54716557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510452590.6A Pending CN105130925A (en) | 2015-07-28 | 2015-07-28 | Preparation method of 2-(Z)-(2-aminothiazol-4-yl)-2-acetoxyiminoacetic acid-2-benzothiazolthioester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105130925A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110759874A (en) * | 2019-10-30 | 2020-02-07 | 广州牌牌生物科技有限公司 | Preparation method of cefdinir impurity A |
-
2015
- 2015-07-28 CN CN201510452590.6A patent/CN105130925A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110759874A (en) * | 2019-10-30 | 2020-02-07 | 广州牌牌生物科技有限公司 | Preparation method of cefdinir impurity A |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103524440B (en) | The preparation method of gout therapertics Lesinurad and Lesinurad intermediate | |
| CN107698513A (en) | A kind of preparation method of sodium ozagrel | |
| CN105130925A (en) | Preparation method of 2-(Z)-(2-aminothiazol-4-yl)-2-acetoxyiminoacetic acid-2-benzothiazolthioester | |
| CN104829590B (en) | Method for purifying trelagliptin | |
| CN110862372B (en) | Synthesis of clopidogrel intermediate (S) -2- (2-thiophenoethylamine) - (2-chlorophenyl) -methyl acetate | |
| CN105524042A (en) | Method for preparing trelagliptin | |
| CN107892676B (en) | The preparation method of Cefdinir active thioester | |
| CN104193616B (en) | The synthetic method of the chloro-5-iodo-benzoic acid of a kind of 2- | |
| CN102336721B (en) | Method for synthesizing AE-active ester by using water-containing 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid | |
| CN103613597A (en) | Preparation process of sildenafil citrate | |
| CN104478974A (en) | Synthesis method of 20,23-dipiperidino-5-O-mycaminose-tylosin lactone | |
| CN104130201A (en) | Preparation method of benzodiazothioketone serving as intermediate of alprazolam | |
| CN104402770B (en) | A kind of preparation method of camostat mesilate intermediate | |
| CN101781311A (en) | Novel preparation method of platelet aggregation inhibition compound | |
| CN102942574B (en) | Novel process for producing rifamycin S | |
| CN105481771B (en) | A kind of preparation process of ozagrel intermediate (E) -4- (imidazolyl methyl) methyl cinnamate | |
| CN105272883B (en) | A kind of preparation method of the fluoro benzoyl acetonitrile of high-purity 4 | |
| CN106588888A (en) | High-purity L-sunitinib malate preparation method | |
| CN105237419B (en) | The method for synthesizing L norvalines | |
| CN104098535A (en) | Preparation method for 4-(3-fluorine phenyl)-2,2-phenyl-5-(4-(methylmercapto-)phenyl) furan-3(2H)-ketone | |
| CN104693110A (en) | Preparation method of composition containing lacidipine | |
| CN102603648B (en) | 2-(p-aminophenyl) process for purification of-5-aminobenzimidazole | |
| CN104447854B (en) | Preparation method of phosphatidic acid sodium | |
| CN102898289B (en) | Method for synthesizing 2-(4-benzylmethoxyphenyl)ethanol medical intermediate | |
| CN102276543A (en) | Method for refining fluconazole |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20151209 |