CN109575048A - A kind of preparation method of Cefotaxime Sodium - Google Patents
A kind of preparation method of Cefotaxime Sodium Download PDFInfo
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- CN109575048A CN109575048A CN201811604072.1A CN201811604072A CN109575048A CN 109575048 A CN109575048 A CN 109575048A CN 201811604072 A CN201811604072 A CN 201811604072A CN 109575048 A CN109575048 A CN 109575048A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/26—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group
- C07D501/34—Methylene radicals, substituted by oxygen atoms; Lactones thereof with the 2-carboxyl group with the 7-amino radical acylated by carboxylic acids containing hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/04—Preparation from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/12—Separation; Purification
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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Abstract
The present invention provides a kind of preparation methods of Cefotaxime Sodium, it is characterised in that: after the active group of silylating reagent protection 7-amino-cephalosporanic acid, condensation reaction occurs with 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic,thiobenzothiazole ester and generates the cefotaxime acid containing protecting group；This contains the cefotaxime acid of protecting group after deprotection agent effect deprotection, successively obtains cefotaxime acid through water phase acidification crystallization；The cefotaxime acid obtains cefotaxime sodium pure product after at salt and solvent crystallization.Entire technical process reduces the degradation process of product, hence it is evident that improves product quality, improves product competitiveness in the market, has further guarantee to drug safety.
Description
Technical field
The present invention relates to organic synthesis fields, and in particular, to a kind of preparation method of antibacterials Cefotaxime Sodium.
Background technique
Cefotaxime Sodium chemical name is (6R, 7R) -3- [(acetoxyl group) methyl] -7- [(2- amino -4- thiazolyl) -
(methoxy imino) acetamido] -8- oxo -5- thia -1- azabicyclo [4.2.0] oct-2-ene -2- carboxylic acid sodium.For third
For injection cephalosporin antibiotic product.
The kind technology is mainly 7-amino-cephalosporanic acid and 2- methoxyimino -2- (2- amino -4- thiazolyl)-at present
(z) in methylene chloride or 2- methyltetrahydrofuran equal solvent cefotaxime acid is added, then in-thioacetic acid phenylhydrazine thiazole ester
The solvents such as Organic Alcohol are added, diluted acid is added dropwise and adjusts PH crystallization, is centrifugally separating to obtain the cefotaxime acid solid after being completely dried.
Later, by by the solid pure product after the drying, in the aqueous solution or sodium iso-octoate organic solvent containing sodium acetate
Cefotaxime Sodium is obtained at sodium salt, then with the solvents crystallization such as acetone or isopropanol.
The above process, due to 7-ACA amino carboxyl etc., more active functional group is unprotected, causes oxidizable in reaction process
Degradation, impurity higher result on the high side.And it is higher to obtain product color grade, is unfavorable for subsequent production, research and utilizes.
Summary of the invention
Present invention aims to overcome that shortcoming present in above-mentioned technology, is first protected using 7-ACA amino and carboxyl
It is condensed into cefotaxime acid with 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic,thiobenzothiazole ester again afterwards, after then addition weak base aqueous solution is deprotected, acidizing crystal, then
Cefotaxime acid at sodium salt, using organic solvent crystallization, obtains quality better than commercially available and former grind in the sodium solution of absolute alcohol
Product.Technical process reduces the discharge of organic matter, and technique is made to become energy conservation and environmental protection, hence it is evident that improves product quality.
In order to achieve the above object, the present invention provides a kind of preparation methods of Cefotaxime Sodium, it is characterised in that: with silicon
After Alkylators protect the active group of 7-amino-cephalosporanic acid, condensation reaction generation occurs with 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic,thiobenzothiazole ester and contains protecting group
Cefotaxime acid；
This contains the cefotaxime acid of protecting group after deprotection agent effect deprotection, successively obtains through water phase acidification crystallization
Cefotaxime acid；
The cefotaxime acid obtains cefotaxime sodium pure product after at salt and solvent crystallization.
Further, the preparation method of a kind of Cefotaxime Sodium provided by the invention, also has a characteristic that
Radical protection reaction exists, using halogenated hydrocarbons as solvent in the environment of carry out；Such as: chloroform, methylene chloride, carbon tetrachloride
Deng.
Above-mentioned deprotection agent be alkali or alkaline earth metal hydroxide, carbonate or bicarbonate (such as: hydroxide
Sodium, potassium hydroxide, sodium carbonate, sodium bicarbonate etc.), one of polyamine (such as: triethylamine, diethylamine, ethylenediamine) or
It is several；
Above-mentioned silylating reagent is selected from two silicon urea of hexamethyl, HMDS, BSA, BSU or the silanization examination with similar structure
Agent；
The reagent of above-mentioned salt-forming reaction is selected from the Organic Sodium Salt that carbon atom number is not more than 20., the general Organic Sodium Salt is alkane
Base acid sodium-salt, such as: sodium acetate or sodium iso-octoate.Preferred such sodium salt dissolves or the miscible progress in alcohols solvent is anti-
It answers.
Further, the preparation method of a kind of Cefotaxime Sodium provided by the invention, also have a characteristic that i.e., tool
Body technology is shown in steps are as follows:
S1. living with AE- after silylating reagent, 7-amino-cephalosporanic acid temperature rising reflux dissolved clarification is added in halogenated hydrocarbon solvent
Property ester shrink at a temperature of 10-30 DEG C, reaction 10-24 hour after, acquisition the cefotaxime acid containing protecting group；
S2. the product of deprotection agent extraction S1 is added, obtains water phase, at 30 DEG C of temperature below of temperature control, pH is adjusted to
Crystallization between 2.8-3.0 obtains cefotaxime acid crude；
Specific reaction equation is as follows:
S3. salt-forming reagent and cefotaxime acid crude are sequentially added, after stirring dissolved clarification, crystalline reagents growing the grain is added.
The optional esters of crystalline reagents (methyl acetate, ethyl acetate etc.), ketone (acetone etc.), ethers, alcohols etc. are highly polar
One or more of solvent miscible agent.
Specific equation is as follows:
Further, the preparation method of a kind of Cefotaxime Sodium provided by the invention, also have a characteristic that i.e., on
The molar ratio for stating 7-amino-cephalosporanic acid and silylating reagent is 1:1.05-2.0；
The molar ratio of above-mentioned 7-amino-cephalosporanic acid and silylating reagent is 1:1.5-2.0；
The weight ratio of above-mentioned 7-amino-cephalosporanic acid and silylating reagent is 1.5-2.0；
The dosage of above-mentioned silylating reagent is the 60%-80% of 7-amino-cephalosporanic acid and 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic,thiobenzothiazole ester total weight；
The mass ratio of above-mentioned 7-amino-cephalosporanic acid and 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic,thiobenzothiazole ester is 1:1-5；
The mass ratio of above-mentioned 7-amino-cephalosporanic acid and deprotection agent is 1:0.5-5；
The additive amount of above-mentioned deprotection agent is adjusted within the scope of 7.0-9.0 with the pH value of reaction system as addition terminal；
The mass ratio of above-mentioned cefotaxime acid and salt-forming reagent is 1:0.3-0.6；
The molar ratio of above-mentioned salt-forming reagent and cefotaxime acid is 1:1.0-2.0.
Further, the preparation method of a kind of Cefotaxime Sodium provided by the invention, also have a characteristic that i.e., on
S2 is stated to carry out at 20 DEG C of temperature below；
Above-mentioned deprotection agent is miscible to be reacted after water；
The dosage of above-mentioned water is 0.3-2.5 times of solvent usage in S1.
Specific steps can be as follows:
S2-1. after reaction, it is cooled to 20 DEG C or less addition sodium bicarbonate/pure water quenching reactions；The dosage of the water is
0.3-2.5 times of solvent usage.
S2-2. after the deprotection of addition aqueous alkali, it is acidified crystallization, be centrifugated and is obtained after washing filtering with detergent wet
Product cefotaxime acid；The process is generally, through after a period of time wash crystalline substance after, solid product is extracted by way of centrifugation, and
It is made a return journey by way of repeatedly washing deimpurity residual, the solvent of washing can be the reagent of the advanced property such as water, alcohol, ketone, ether.
Or
S2-1. after reaction, it is cooled to 20 DEG C or less addition pure water quenching reactions；
S2-2. active carbon decoloring 5-30min；
S2-3. it after addition aqueous alkali acidification crystallization, is centrifugated and obtains wet product cephalo after washing filtering with detergent
Thiophene oxime acid.
Above-mentioned detergent be selected from pure water, ketones solvent (acetone etc.), alcohols solvent (methanol, ethyl alcohol, propyl alcohol, butanol etc.),
The one or more of (ether, second diether, tetrahydrofuran, dioxane etc.) in ether solvent.
Further, the preparation method of a kind of Cefotaxime Sodium provided by the invention, also have a characteristic that i.e.,
The cosolvent, acylation catalyst or activator for accounting for 0.01-1 times of reactant total weight are also added in S2.
Such as: CDI, EDCI, DIC, DCC, DMAP, HOBt, DMF, DMA, HATU, HBTU, NMM, TFA, TEA reagent.
Further, the preparation method of a kind of Cefotaxime Sodium provided by the invention, also have a characteristic that i.e., on
The step of stating S3 is in dimethyl carbonate, methylene chloride, chloroform, carbon tetrachloride, tetrahydrofuran, ethyl alcohol, methanol, acetone, just
The in the mixed solvent of one or more of butanol, triethylamine, diethylamine, water, DMF, ethyl acetate, isopropanol carries out；
Above-mentioned salt forming agent carries out salt-forming reaction after mixing with alcohol；
The dosage of above-mentioned alcohol is 2.0-4.0 times of cefotaxime acid.
Concrete processing procedure in above-mentioned S3 can be as follows:
S3-1. the alcoholic solution of cefotaxime acid and sodium is at salt；The dosage of the alcohol is 2.0-4.0 times of cefotaxime acid.
S3-2. above-mentioned cefotaxime sodium solution muddiness crystallization is added dropwise with organic solvent.The organic solvent used is molten for ketone
One or more of agent, alcohols solvent, esters solvent crystallization obtain target product.
Or
S3-1. after the alcoholic solution of cefotaxime acid and sodium is at salt, organic solvent crystallization is added；
S3-2. active carbon decoloring 5-30min；
S3-3. crystallization is added dropwise with organic solvent, using one or more of ketones solvent, alcohols solvent, esters solvent
Crystallization obtains target product.
Solvent in above-mentioned reaction process can be selected from dimethyl carbonate, methylene chloride, chloroform, carbon tetrachloride, tetrahydro
Furans, ethyl alcohol, methanol, acetone, n-butanol, triethylamine, diethylamine, water, DMF, ethyl acetate, isopropanol etc..
Further, the preparation method of a kind of Cefotaxime Sodium provided by the invention, also have a characteristic that i.e., on
It states organic solvent and is selected from one or more of ketones solvent, alcohols solvent, esters solvent.
Further, the preparation method of a kind of Cefotaxime Sodium provided by the invention, also have a characteristic that i.e., on
During stating S2 and S3, also by the process of active carbon decoloring.
The function and effect of the present invention:
Content of Cefotaxime Sodium using the method for the present invention production is high, and color grade is good, it is known that impurity is less than original and grinds and list production
Product, unknown impuritie can be controlled in 0.05% or less；In the method for the invention, it is tried before synthesizing cefotaxime acid with silanization
Agent first to 7-amino-cephalosporanic acid carry out amino carboxy protective, synthesize Cefotaxime Sodium when in anhydrous conditions cefotaxime acid with
Sodium is at salt, then carries out solvent crystallization, obtains Cefotaxime Sodium product.Entire technical process reduces the degradation process of product, bright
It is aobvious to improve product quality, product competitiveness in the market is improved, has further guarantee to drug safety.
Detailed description of the invention
The map of Fig. 1 embodiment 1-1；
The map of Fig. 2 embodiment 1-2；
The map of Fig. 3 embodiment 2-1；
The map of Fig. 4 embodiment 2-2；
The map of Fig. 5 embodiment 3-1；
The map of Fig. 6 embodiment 3-2.
Specific embodiment
Embodiment 1-1,
Chloroform 500ml, 7-amino-cephalosporanic acid 20g, HMDS22g are added at room temperature.Heating is heated to reflux 5-
Then 6.0hr is cooled to 20 DEG C or less addition 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic,thiobenzothiazole ester 28g condensation 12-15hr.
Then the sodium bicarbonate aqueous solution 300ml of addition 8% is extracted, and 2g activity carbon decoloring 20min mistake is added in water phase
Filter.By 30 DEG C of filtrate temperature control hereinafter, acetone 130ml, n-butanol 65ml is added, dilute acid soln tune PH2.8-3.0 is added dropwise, is precipitated brilliant
Body.Filtering, filter cake pure water use acetone washing again after draining, the dry cefotaxime acid crude that discharges to obtain, yield after draining
85%.
High pressure liquid phase purity 99.6%, color yellow green≤2#.(being detailed in attached drawing 1)
Embodiment 1-2,
Anhydrous methanol 300ml is added in reactor, sodium acetate 15g, stirring and dissolving is added.Then it is thick that cefotaxime acid is added
Product 45g stirs dissolved clarification.Active carbon 2g is added, decolourize 20min, filtering.Filtrate added drop-wise acetone is to muddiness.Growing the grain 60min.Then
Later period acetone is added dropwise, is cooled to 0-5 DEG C, growing the grain 60min.It filters, dry Cefotaxime Sodium, yield 87%.
High pressure liquid phase purity 99.6%, color yellow green≤2#.(being detailed in attached drawing 2)
Embodiment 2-1,
Methylene chloride 300ml, 7-amino-cephalosporanic acid 20g, BSU 35g are added at room temperature.Heating is heated to reflux 5-
Then 6.0hr is cooled to 20 DEG C or less addition 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic,thiobenzothiazole ester 30g condensation 12-15hr.
Then the sodium hydrate aqueous solution 200ml of addition 6% is extracted, and 2g activity carbon decoloring 20min mistake is added in water phase
Filter.By 30 DEG C of filtrate temperature control hereinafter, tetrahydrofuran 130ml, n-butanol 65ml is added, dilute acid soln tune PH2.8-3.0, analysis is added dropwise
Crystal out.Filtering, filter cake pure water are washed with tetrahydrofuran again after draining, the dry cefotaxime acid that discharges to obtain after draining
Crude product, yield 88%.
High pressure liquid phase purity 99.6%, color yellow green≤2#.(being detailed in attached drawing 3)
Embodiment 2-2,
Ethyl alcohol 150ml is added in reactor, sodium iso-octoate 26g, stirring and dissolving is added.Then cefotaxime acid crude is added
Appropriate triethylamine is added dropwise in 45g, stirs dissolved clarification.Active carbon 2g is added, decolourize 20min, filtering.Filtrate added drop-wise ethyl alcohol is to muddiness.It supports
Brilliant 60min.Then later period ethyl alcohol is added dropwise, is cooled to 0-5 DEG C, growing the grain 60min.It filters, dry Cefotaxime Sodium, yield
86%.
High pressure liquid phase purity 99.5%, color yellow green≤2#.(being detailed in attached drawing 4)
Embodiment 3-1,
Methylene chloride 300ml, carbon tetrachloride 150ml, 7-amino-cephalosporanic acid 20g, BSA 30g are added at room temperature.Heating
It is heated to reflux 5-6.0hr, is then cooled to 20 DEG C or less addition 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic,thiobenzothiazole ester 28g condensation 12-15hr.
Then the aqueous sodium carbonate 270ml of addition 10% is extracted, and 2g activity carbon decoloring 20min mistake is added in water phase
Filter.By 30 DEG C of filtrate temperature control hereinafter, tetrahydrofuran 130ml, isopropanol 65ml is added, dilute acid soln tune PH2.8-3.0, analysis is added dropwise
Crystal out.Filtering, filter cake pure water are washed with tetrahydrofuran, isopropanol again after draining, the dry cephalo that discharges to obtain after draining
Thiophene oxime acid crude, yield 88%.
High pressure liquid phase purity 99.6%, color yellow green≤2#.(being detailed in attached drawing 5)
Embodiment 3-2,
Anhydrous methanol 200ml is added in reactor, sodium iso-octoate 26g, stirring and dissolving is added.Then cefotaxime acid is added
Crude product 45g stirs dissolved clarification.Active carbon 2g is added, decolourize 20min, filtering.Filtrate added drop-wise ethyl acetate is to muddiness.Growing the grain
60min.Then ethyl acetate is added dropwise, is cooled to 0-5 DEG C, growing the grain 60min.It filters, dry Cefotaxime Sodium, yield 87%.
High pressure liquid phase purity 99.6%, color yellow green≤2#.(being detailed in attached drawing 6).
Claims (10)
1. a kind of preparation method of Cefotaxime Sodium, it is characterised in that: with the work of silylating reagent protection 7-amino-cephalosporanic acid
Property group after, with 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic,thiobenzothiazole ester occur condensation reaction generate the cefotaxime acid containing protecting group；
This contains the cefotaxime acid of protecting group after deprotection agent effect deprotection, successively obtains cephalo through water phase acidification crystallization
Thiophene oxime acid；
The cefotaxime acid obtains cefotaxime sodium pure product after at salt and solvent crystallization.
2. a kind of preparation method of Cefotaxime Sodium as described in claim 1, it is characterised in that:
Radical protection reaction exists, using halogenated hydrocarbons as solvent in the environment of carry out；
The deprotection agent is hydroxide, carbonate or the bicarbonate of alkali or alkaline earth metal, one of polyamine
Or it is several；
The silylating reagent is selected from two silicon urea of hexamethyl, HMDS, BSA, BSU or the silylating reagent with similar structure；
The reagent of the salt-forming reaction is selected from the Organic Sodium Salt that carbon atom number is not more than 20.
3. a kind of preparation method of Cefotaxime Sodium as described in claim 1, which is characterized in that the following institute of specific process step
Show:
S1. in halogenated hydrocarbon solvent, after silylating reagent, 7-amino-cephalosporanic acid temperature rising reflux dissolved clarification is added, with 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic,thiobenzothiazole ester
It shrinks at a temperature of 10-30 DEG C, after reaction 10-24 hours, obtains the cefotaxime acid containing protecting group；
S2. the product of deprotection agent extraction S1 is added, obtains water phase, at 30 DEG C of temperature below of temperature control, pH is adjusted to 2.8-
Crystallization between 3.0 obtains cefotaxime acid crude；
S3. salt-forming reagent and cefotaxime acid crude are sequentially added, after stirring dissolved clarification, crystalline reagents growing the grain is added.
4. a kind of preparation method of Cefotaxime Sodium as claimed in claim 4, it is characterised in that:
The molar ratio of the 7-amino-cephalosporanic acid and silylating reagent is 1:1.05-2.0；
The molar ratio of the 7-amino-cephalosporanic acid and silylating reagent is 1:1.5-2.0；
The weight ratio of the 7-amino-cephalosporanic acid and silylating reagent is 1.5-2.0；
The dosage of the silylating reagent is the 60%-80% of 7-amino-cephalosporanic acid and 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic,thiobenzothiazole ester total weight；
The mass ratio of the 7-amino-cephalosporanic acid and 2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetic,thiobenzothiazole ester is 1:1-5；
The mass ratio of the 7-amino-cephalosporanic acid and deprotection agent is 1:0.5-5；
It is addition terminal that the additive amount of the deprotection agent, which is within the scope of 7.0-9.0 with the pH value of reaction system,；
The mass ratio of the cefotaxime acid and salt-forming reagent is 1:0.3-0.6；
The molar ratio of the salt-forming reagent and cefotaxime acid is 1:1.0-2.0.
5. a kind of preparation method of Cefotaxime Sodium as claimed in claim 4, it is characterised in that:
The S2 is carried out at 20 DEG C of temperature below；
The deprotection agent is miscible to be reacted after water；
The dosage of the water is 0.3-2.5 times of solvent usage in S1.
6. a kind of preparation method of Cefotaxime Sodium as claimed in claim 4, it is characterised in that:
The crystal of precipitation in the S2 is carried out at least once using one or more of water, alcohols, ketone, ether solvent
Washing.
7. a kind of preparation method of Cefotaxime Sodium as claimed in claim 4, it is characterised in that:
The step of S3, is in dimethyl carbonate, methylene chloride, chloroform, carbon tetrachloride, tetrahydrofuran, ethyl alcohol, methanol, third
The in the mixed solvent of one or more of ketone, n-butanol, triethylamine, diethylamine, water, DMF, ethyl acetate, isopropanol carries out；
The salt forming agent carries out salt-forming reaction after mixing with alcohol；
The dosage of the alcohol is 2.0-4.0 times of cefotaxime acid.
8. a kind of preparation method of Cefotaxime Sodium as claimed in claim 4, it is characterised in that:
The organic solvent is selected from one or more of ketones solvent, alcohols solvent, esters solvent.
9. a kind of preparation method of Cefotaxime Sodium as claimed in claim 4, it is characterised in that:
The cosolvent, acylation catalyst or activator for accounting for 0.01-1 times of reactant total weight are also added in the S3.
10. a kind of preparation method of Cefotaxime Sodium as claimed in claim 4, it is characterised in that:
During the S2 and S3, also by the process of active carbon decoloring.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110283187A (en) * | 2019-07-10 | 2019-09-27 | 辽宁美亚制药有限公司 | A kind of preparation method promoting Cefotaxime Sodium product quality |
| CN111647006A (en) * | 2020-04-25 | 2020-09-11 | 广东金城金素制药有限公司 | Cefotaxime sodium pharmaceutical preparation and new indications for treating salmonella infection including typhoid fever and paratyphoid fever |
| CN114989194A (en) * | 2022-06-07 | 2022-09-02 | 艾美科健（中国）生物医药有限公司 | Method for effectively reducing polymer in cefotaxime sodium |
| CN115232151A (en) * | 2022-08-04 | 2022-10-25 | 辽宁美亚制药有限公司 | New synthesis method of ceftriaxone sodium |
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| CN110283187A (en) * | 2019-07-10 | 2019-09-27 | 辽宁美亚制药有限公司 | A kind of preparation method promoting Cefotaxime Sodium product quality |
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| CN111647006B (en) * | 2020-04-25 | 2021-06-08 | 广东金城金素制药有限公司 | Cefotaxime sodium pharmaceutical preparation and treatment of salmonella infection indications including typhoid fever and paratyphoid fever |
| CN114989194A (en) * | 2022-06-07 | 2022-09-02 | 艾美科健（中国）生物医药有限公司 | Method for effectively reducing polymer in cefotaxime sodium |
| CN114989194B (en) * | 2022-06-07 | 2023-09-26 | 艾美科健（中国）生物医药有限公司 | Method for reducing polymer in cefotaxime sodium |
| CN115232151A (en) * | 2022-08-04 | 2022-10-25 | 辽宁美亚制药有限公司 | New synthesis method of ceftriaxone sodium |
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