CN107573305A - A kind of preparation method of SMIA - Google Patents
A kind of preparation method of SMIA Download PDFInfo
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- CN107573305A CN107573305A CN201710762604.3A CN201710762604A CN107573305A CN 107573305 A CN107573305 A CN 107573305A CN 201710762604 A CN201710762604 A CN 201710762604A CN 107573305 A CN107573305 A CN 107573305A
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- furans
- smia
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- acid
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Abstract
The invention discloses a kind of preparation method of SMIA, comprise the following steps：Using 2 acetyl furans as raw material, under the catalytic action of metal salt, furans ketone acid is made in 2 acetyl furans and natrium nitrosum reaction；Furans ketone acid and alcohol are esterified generation furans keto ester in the presence of the concentrated sulfuric acid；Step furans keto ester and methoxamine are reacted to obtain the furans methyl acetate of 2 methoxy imino 2；After the pH value regulation of the furans methyl acetate solution of 2 methoxy imino 2 the furans acetic acid solution of 2 methoxy imino 2 will be extracted to obtain with organic solvent；The furans acetic acid solution of 2 methoxy imino 2 and alcohol ammonia solvent are reacted, obtain SMIA.Metal salt in the step S1 is molysite, the one or more in the sulfate of mantoquita, zinc salt.One aspect of the present invention improves the yield of SMIA by improving the conversion ratio of acetyl furan, on the other hand improves the yield of SMIA by reducing the content of trans SMIA.
Description
Technical field
The present invention relates to a kind of SMIA preparation technology, and in particular to a kind of preparation method of SMIA.
Background technology
Cephalosporin analog antibiotic Cefuroxime Sodium and Cefuroxime have the effect of good at present, and the dosage of these medicines is got over
Come bigger, and SMIA is as a kind of Medicine intermediate, and is synthesis second generation cephalosporins medicine cefuroxime again
Key intermediate, synthetic technology is not still very ripe at home for the product, and yield is also very low.SMIA in existing market very
It is good, the market demand of the country can not be met in yield and quality.Therefore, such product production and application exist it is very big
Development space
Relate to the preparation method of SMIA in the prior art, common method be by 2- oxos -2- furans guanidine-acetic acid with
The direct reaction of methoxamine prepares SMIA, and the yield of the method is low；Common method also includes using 2- acetyl furans as raw material system
Standby SMIA, but in the prior art 2- acetyl furans be converted into furans ketone acid conversion ratio it is low so that SMIA
Yield is low.
The content of the invention
The technical problems to be solved by the invention are to prepare SMIA using 2- acetyl furans as raw material in the prior art
Yield is low, and it is an object of the present invention to provide a kind of preparation method of SMIA, solves to prepare SMIA using 2- acetyl furans as raw material
When, the problem of yield of SMIA is low.
The present invention is achieved through the following technical solutions：
A kind of preparation method of SMIA, comprises the following steps：
S1, using 2- acetyl furans as raw material, under the catalytic action of metal salt, 2- acetyl furans and natrium nitrosum reaction system
Obtain furans ketone acid；
S2, the furans ketone acid and alcohol that are obtained in step S1 are esterified to generation furans keto ester in the presence of the concentrated sulfuric acid；
S3, the furans keto ester and methoxamine that obtain in step S2 reacted to obtain 2- methoxy imino -2- furans acetic acid first
Ester；
S4, at 25 DEG C with alkaline solution by the 2- methoxy imino -2- furans methyl acetate solution obtained in step S3
Insulated and stirred 5-6 hours after pH value is adjusted to 8-9, extracted with salt acid for adjusting pH to 6.5-7 with organic solvent after insulated and stirred
2- methoxy imino -2- furans acetic acid solutions；
S5, by the 2- methoxy iminos -2- furans acetic acid solution and alcohol ammonia solvent that are obtained in step S4 react, obtain furans ammonium
Salt.Metal salt in the step S1 is molysite, the one or more in the sulfate of mantoquita, zinc salt.
The present invention is catalyzed using metal salt to acetyl furan, is improved the conversion ratio of acetyl furan, is favorably improved
The yield of SMIA；The present invention using 2- acetyl furans as raw material, oxidative synthesis furans ketone acid, be then esterified, then with methoxamine
Reaction, synthesizing methoxy oximate product, is then hydrolyzed, and reacts to obtain SMIA with alcohol ammonia solvent, of the invention by furans ketone acid
First it is esterified, improves the activity of carbonyl, promote oximated product to be more converted into cis-product, the trans SMIA being prepared
Content be only 5%-8%, compared with traditional mode of production SMIA method, the content of trans SMIA significantly reduces, furans
The content of ammonium salt significantly improves, so as to improve the yield of SMIA.One aspect of the present invention is by improving turning for acetyl furan
Rate improves the yield of SMIA, on the other hand improves the receipts of SMIA by reducing the content of trans SMIA
Rate.
The reaction temperature of acetyl furan and natrium nitrosum is 90-100 DEG C in step S1, and the reaction time is 3-4 hours, described
The pH value of furans ketone acid is 1-2.The preferred optimum reaction condition of acetyl furan and natrium nitrosum of the present invention.
The mol ratio of furans keto ester and methoxamine is 1 in the step S3:1.3-1.8.The micro- excess of dosage of methoxamine,
Furans keto ester is changed completely as far as possible.
The mol ratio of furans keto ester and methoxamine is 1 in the step S3:1.5.The preferred optimum proportioning of the present invention.
The present invention compared with prior art, has the following advantages and advantages：
1st, a kind of preparation method of SMIA of the present invention improves SMIA by improving the conversion ratio of acetyl furan
Yield；
2nd, a kind of preparation method of SMIA of the present invention is further improved by reducing the content of trans SMIA
The yield of SMIA；
3rd, a kind of preparation method of SMIA of the present invention is simple, and product purity, yield are high.
Embodiment
For the object, technical solutions and advantages of the present invention are more clearly understood, with reference to embodiment, the present invention is made
Further to describe in detail, exemplary embodiment of the invention and its explanation are only used for explaining the present invention, are not intended as to this
The restriction of invention.
Embodiment 1
A kind of preparation method of SMIA of the present invention, comprises the following steps：
S1, using 2- acetyl furans as raw material, under the catalytic action of metal salt, 2- acetyl furans and natrium nitrosum reaction system
Obtain furans ketone acid；
S2, the furans ketone acid and alcohol that are obtained in step S1 are esterified to generation furans keto ester in the presence of the concentrated sulfuric acid；
S3, the furans keto ester and methoxamine that obtain in step S2 reacted to obtain 2- methoxy imino -2- furans acetic acid first
Ester；
S4, at 25 DEG C with alkaline solution by the 2- methoxy imino -2- furans methyl acetate solution obtained in step S3
Insulated and stirred 5-6 hours after pH value is adjusted to 8-9, extracted with salt acid for adjusting pH to 6.5-7 with organic solvent after insulated and stirred
2- methoxy imino -2- furans acetic acid solutions；
S5, by the 2- methoxy iminos -2- furans acetic acid solution and alcohol ammonia solvent that are obtained in step S4 react, obtain furans ammonium
Salt.Metal salt in the step S1 is molysite, the one or more in the sulfate of mantoquita, zinc salt.
The reaction temperature of acetyl furan and natrium nitrosum is 90-100 DEG C in step S1, and the reaction time is 3-4 hours, described
The pH value of furans ketone acid is 1-2.The preferred optimum reaction condition of acetyl furan and natrium nitrosum of the present invention.In the step S3
The mol ratio of furans keto ester and methoxamine is 1:1.3-1.8.The micro- excess of dosage of methoxamine, furans keto ester is as complete as possible
Full conversion.
The present invention is catalyzed using metal salt to acetyl furan, is improved the conversion ratio of acetyl furan, is favorably improved
The yield of SMIA；The present invention using 2- acetyl furans as raw material, oxidative synthesis furans ketone acid, be then esterified, then with methoxamine
Reaction, synthesizing methoxy oximate product, is then hydrolyzed, and reacts to obtain SMIA with alcohol ammonia solvent, of the invention by furans ketone acid
First it is esterified, improves the activity of carbonyl, promote oximated product to be more converted into cis-product, the trans SMIA being prepared
Content be only 5%-8%, compared with traditional mode of production SMIA method, the content of trans SMIA significantly reduces, furans
The content of ammonium salt significantly improves, so as to improve the yield of SMIA.One aspect of the present invention is by improving turning for acetyl furan
Rate improves the yield of SMIA, on the other hand improves the receipts of SMIA by reducing the content of trans SMIA
Rate.
Embodiment 2
Based on embodiment 1, the mol ratio of furans keto ester and methoxamine is 1 in the step S3:1.5.It is of the invention preferred
Optimum proportioning.The high income of SMIA of the present invention is up to more than 90%.
Above-described embodiment, the purpose of the present invention, technical scheme and beneficial effect are carried out further
Describe in detail, should be understood that the embodiment that the foregoing is only the present invention, be not intended to limit the present invention
Protection domain, within the spirit and principles of the invention, any modification, equivalent substitution and improvements done etc., all should include
Within protection scope of the present invention.
Claims (5)
1. a kind of preparation method of SMIA, it is characterised in that comprise the following steps：
S1, using 2- acetyl furans as raw material, under the catalytic action of metal salt, 2- acetyl furans and natrium nitrosum reaction be made furan
Mutter ketone acid；
S2, the furans ketone acid and alcohol that are obtained in step S1 are esterified to generation furans keto ester in the presence of the concentrated sulfuric acid；
S3, the furans keto ester and methoxamine that obtain in step S2 reacted to obtain 2- methoxy imino -2- furans methyl acetates；
S4, at 25 DEG C with alkaline solution by the pH value of the 2- methoxy imino -2- furans methyl acetate solution obtained in step S3
Regulation extracts to obtain 2- first to insulated and stirred 5-6 hours after 8-9 to 6.5-7 with salt acid for adjusting pH after insulated and stirred with organic solvent
Oxygen imines -2- furans acetic acid solutions；
S5, by the 2- methoxy iminos -2- furans acetic acid solution and alcohol ammonia solvent that are obtained in step S4 react, obtain SMIA.
A kind of 2. preparation method of SMIA according to claim 1, it is characterised in that the metal in the step S1
Salt is the one or more in the sulfate of molysite, mantoquita, zinc salt.
A kind of 3. preparation method of SMIA according to claim 1 or 2, it is characterised in that acetyl furan in step S1
It is 90-100 DEG C to mutter with the reaction temperature of natrium nitrosum, and the reaction time is 3-4 hours, and the pH value of the furans ketone acid is 1-2.
A kind of 4. preparation method of SMIA according to claim 1, it is characterised in that furanone in the step S3
The mol ratio of acid esters and methoxamine is 1:1.3-1.8.
A kind of 5. preparation method of SMIA according to claim 4, it is characterised in that furanone in the step S3
The mol ratio of acid esters and methoxamine is 1:1.5.
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| CN201710762604.3A CN107573305A (en) | 2017-08-30 | 2017-08-30 | A kind of preparation method of SMIA |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110003043A (en) * | 2019-04-28 | 2019-07-12 | 山东金城医药化工有限公司 | The method of methoxamine is recycled from furan ammonium salt waste water |
| CN113999194A (en) * | 2021-11-22 | 2022-02-01 | 山东金城医药化工有限公司 | Process for the preparation of furan ammonium salts |
| CN114014823A (en) * | 2021-12-15 | 2022-02-08 | 山东金城医药化工有限公司 | Preparation method of trans-ethyl noraminothiazolyloximate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102863407A (en) * | 2012-10-10 | 2013-01-09 | 山东金城医药化工股份有限公司 | Preparation method of 2-methoxyiminofurylacetic acid amonium salt |
| CN105254603A (en) * | 2015-10-12 | 2016-01-20 | 山东金城医药化工股份有限公司 | Synthetic technology of furan ammonium salt |
| CN105330627A (en) * | 2015-11-24 | 2016-02-17 | 辽宁大学 | Method for preparing syn-2-methoxyimino-2-(furyl-2-yl) acetic acid ammonium salt at high selectivity |
-
2017
- 2017-08-30 CN CN201710762604.3A patent/CN107573305A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102863407A (en) * | 2012-10-10 | 2013-01-09 | 山东金城医药化工股份有限公司 | Preparation method of 2-methoxyiminofurylacetic acid amonium salt |
| CN105254603A (en) * | 2015-10-12 | 2016-01-20 | 山东金城医药化工股份有限公司 | Synthetic technology of furan ammonium salt |
| CN105330627A (en) * | 2015-11-24 | 2016-02-17 | 辽宁大学 | Method for preparing syn-2-methoxyimino-2-(furyl-2-yl) acetic acid ammonium salt at high selectivity |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110003043A (en) * | 2019-04-28 | 2019-07-12 | 山东金城医药化工有限公司 | The method of methoxamine is recycled from furan ammonium salt waste water |
| CN110003043B (en) * | 2019-04-28 | 2021-12-14 | 山东金城医药化工有限公司 | Method for recovering methoxyamine from furan ammonium salt wastewater |
| CN113999194A (en) * | 2021-11-22 | 2022-02-01 | 山东金城医药化工有限公司 | Process for the preparation of furan ammonium salts |
| CN113999194B (en) * | 2021-11-22 | 2023-09-12 | 山东金城医药化工有限公司 | Process for the preparation of furan ammonium salts |
| CN114014823A (en) * | 2021-12-15 | 2022-02-08 | 山东金城医药化工有限公司 | Preparation method of trans-ethyl noraminothiazolyloximate |
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Application publication date: 20180112 |