CN108610352A - A kind of method that solvent crystal prepares mezlocillin sodium - Google Patents
A kind of method that solvent crystal prepares mezlocillin sodium Download PDFInfo
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- CN108610352A CN108610352A CN201810603658.XA CN201810603658A CN108610352A CN 108610352 A CN108610352 A CN 108610352A CN 201810603658 A CN201810603658 A CN 201810603658A CN 108610352 A CN108610352 A CN 108610352A
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- Prior art keywords
- mezlocillin
- sodium
- acetone
- present
- solvent
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/21—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a nitrogen atom directly attached in position 6 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D499/44—Compounds with an amino radical acylated by carboxylic acids, attached in position 6
- C07D499/48—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical
- C07D499/58—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical substituted in alpha-position to the carboxamido radical
- C07D499/64—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical substituted in alpha-position to the carboxamido radical by nitrogen atoms
- C07D499/68—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical substituted in alpha-position to the carboxamido radical by nitrogen atoms with aromatic rings as additional substituents on the carbon chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/04—Preparation
- C07D499/14—Preparation of salts
- C07D499/16—Preparation of salts of alkali or alkaline earth metals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/04—Preparation
- C07D499/18—Separation; Purification
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention provides a kind of solvent crystals to prepare mezlocillin sodium method, including following preparation process：1) mezlocillin, acetone, water and sodium iso-octoate are mixed to get mixed liquor；2) after mixed liquor heating up mezlocillin sodium is mixed to get with acetone.The present invention is by being used only same solvent in entire technical process, the product mezlocillin sodium yield for solving the problems, such as mixed solvent, and obtaining is up to 80~95%, purity 99.2~99.8%, and total miscellaneous 0.05~0.15%.
Description
Technical field
The present invention relates to a kind of methods that technical field of medicine synthesis more particularly to solvent crystal prepare mezlocillin sodium.
Background technology
Mezlocillin sodium, English name mezlocillinsodium are one of national essential drugs, belong to the third generation half
Syncillin class antibacterials are a kind of irreversible beta-lactamase inhibitors, to escherichia coli, proteus, copper
Green pseudomonad, Klebsiella Pneumoniae, Enterobacter, neisseria gonorrhoeae, Neisseria meningitidis, streptococcus and bacteroid
Category etc. has antibacterial action.Mezlocillin sodium has very strong anti-infectious function, for treating lower respiratory tract infection, skin sense
Dye, urinary system infection contamination, intraperitoneal infection etc..
The preparation method of mezlocillin for injection mainly has freeze-drying, solvent crystallization, solventing-out process 3 at present
Kind.Wherein solvent crystallization refers to dissolving product suitable medium (be typically all organic solvent) is inner, then passes through reduction
The conditions such as temperature or the amount of reduction solvent make product reach hypersaturated state in solvent, to which the crystallization of product slowly be precipitated
Journey.The method is affected between having used the various vehicle components of double solvent in process of production with comparison crystal structure process,
And it is unfavorable for solvent recycling.
Invention content
In view of this, present invention aims at provide a kind of method that solvent crystal prepares mezlocillin sodium, whole process
Using only same solvent, it is conducive to solvent and recycles, solve the problems, such as mixed solvent.
In order to achieve the above-mentioned object of the invention, the present invention provides following technical scheme：
A kind of solvent crystal prepares mezlocillin sodium method, includes the following steps：
1) mezlocillin, acetone, water and sodium iso-octoate are subjected to neutralization reaction, obtain reaction solution；
2) it is mixed with acetone after the reaction solution that the step (1) obtains heating up, obtains mezlocillin sodium.
Preferably, the amount ratio of mezlocillin in the step 1), acetone, water and sodium iso-octoate is 1kg：3~8L：
0.1-1kg：0.2~0.5kg.
Preferably, in the step 2), the amount ratio of acetone and mezlocillin in step 1) is 3-9L:1kg.
Preferably, the temperature after the reaction solution heating is 10~40 DEG C.
Preferably, the source of the mezlocillin includes the mezlocillin for meeting intermediate quality standard
Advantageous effects：Mezlocillin sodium method is prepared the present invention provides a kind of solvent crystal, and the present invention will will be beautiful
Lip river XiLin acid, acetone, water and sodium iso-octoate carry out neutralization reaction, obtain reaction solution.It mixes, obtains with acetone after reaction solution heating
Mezlocillin sodium.Same solvent acetone is used only in whole process, and solvent recycling (is by moisture height, the underproof acetone of content
The high acetone of the low content of acetone of moisture is obtained by rectifying column rectifying, for producing).Solve the problems, such as mixed solvent, and
And obtained product mezlocillin sodium yield is up to 80~95%, purity 99.2~99.8%, total miscellaneous 0.05~0.15%.
Specific implementation mode
The present invention provides a kind of solvent crystals to prepare mezlocillin sodium method, includes the following steps：
1) mezlocillin, acetone, water and sodium iso-octoate are subjected to neutralization reaction, obtain reaction solution；
2) it is mixed with acetone after the reaction solution that the step 1) obtains heating up, obtains mezlocillin sodium.
Mezlocillin, acetone, water and sodium iso-octoate are carried out neutralization reaction by the present invention, obtain reaction solution；
In the present invention, the amount ratio of the mezlocillin, acetone, water and sodium iso-octoate is 1kg：3~8L：0.1-
1kg：0.2~0.5kg, more preferably 1kg：5~7L：0.3-0.7kg：0.2-0.5kg.
In the present invention, the water is preferably purified water.
Mezlocillin dissolving is preferably formed mezlocillin acetone soln by the specific present invention in acetone, then again
Water is added to be stirred, adds sodium iso-octoate and carries out neutralization reaction.
In the present invention, the rate of the stirring is preferably 20~50Hz, more preferably 45Hz, and the time of stirring is preferably
30min~50min, more preferably 35min~45min.
In the present invention, it is preferred to be added after mezlocillin dissolving is formed mezlocillin acetone soln in acetone
Water.Sodium iso-octoate is added, generates mezlocillin sodium.
In the present invention, the reaction temperature of the neutralization reaction is preferably room temperature；The time of the neutralization reaction is preferably
30min~120min, more preferably 60min.In the present invention, when the time of the neutralization reaction is completely dissolved with sodium iso-octoate
Start to calculate.
In the present invention, the source of the mezlocillin includes the mezlocillin for meeting intermediate quality standard.
After obtaining reaction solution, is mixed with acetone after reaction solution heating of the present invention, obtain mezlocillin sodium.
In the present invention, the mass ratio of the mezlocillin and acetone is preferably 1kg：3~8L, more preferably 1kg：
7L。
In the present invention, preferably 25~35 DEG C, more preferably 28~30 DEG C of the reacting liquid temperature control.
In the present invention, after the mezlocillin sodium crystallization, crystal solution is filtered, obtained solid is dried to obtain Mei Luoxi
Woods sodium finished product.
In the present invention, the temperature of the drying is preferably 30~80 DEG C, more preferably 50-70 DEG C, the drying when
Between preferably 1~6 hour, more preferably 2-4 hours.
For a better understanding of the present invention, with reference to the embodiment content that the present invention is furture elucidated, but the present invention
Content is not limited solely to the following examples.
Embodiment 1
After putting into mezlocillin 134kg addition 670L acetone solutions, it is added after 134kg purified waters stirring half an hour is added
40.2kg sodium iso-octoates are completely dissolved 25 DEG C of rear temperature control, add 1200L acetone, stir mezlocillin sodium crystal after half an hour
It is precipitated, goes out mezlocillin sodium product 131kg after filtration washing drying.Product yield 94%, purity 99.78%, total miscellaneous 0.2%.
Embodiment 2
After putting into mezlocillin 134kg addition 402L acetone solutions, it is added after 67kg purified waters stirring half an hour is added
46.9kg sodium iso-octoates are completely dissolved 27 DEG C of rear temperature control, add 804L acetone, stir mezlocillin sodium crystal analysis after half an hour
Go out, goes out mezlocillin sodium product 133.9kg after filtration washing drying.Product yield 96%, purity 99.82%, total miscellaneous 0.2%.
Embodiment 3
After putting into mezlocillin 134kg addition 1072L acetone solutions, add after 13.4kg purified waters stirring half an hour is added
Enter 43.3kg sodium iso-octoates, be completely dissolved 30 DEG C of rear temperature control, add 410L acetone, stirs mezlocillin sodium crystal after half an hour
It is precipitated, goes out mezlocillin sodium product 129.4kg after filtration washing drying.Product yield 92.78%, purity 99.91 are total miscellaneous
0.1%.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (5)
1. a kind of solvent crystal prepares mezlocillin sodium method, include the following steps：
1) mezlocillin, acetone, water and sodium iso-octoate are subjected to neutralization reaction, obtain reaction solution；
2) it is mixed with acetone after the reaction solution that the step (1) obtains heating up, obtains mezlocillin sodium.
2. according to the method described in claim 1, it is characterized in that, in the step 1), mezlocillin, acetone, water with it is different
The amount ratio of Sodium Caprylate is 1kg：3~8L：0.1-1kg：0.2~0.5kg.
3. according to the method described in claim 1, it is characterized in that, mezlocillin in acetone and step 1) in the step 2)
Mass ratio be 3-9L：1kg.
4. according to the method described in claim 1, it is characterized in that, in the step 2), the temperature after reaction solution heating is 10
~40 DEG C.
5. according to the method described in claim 1, it is characterized in that, the source of the mezlocillin includes meeting intermediate constitution
The mezlocillin of amount standard.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810603658.XA CN108610352B (en) | 2018-06-12 | 2018-06-12 | Method for preparing mezlocillin sodium by solvent crystallization |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810603658.XA CN108610352B (en) | 2018-06-12 | 2018-06-12 | Method for preparing mezlocillin sodium by solvent crystallization |
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| CN108610352A true CN108610352A (en) | 2018-10-02 |
| CN108610352B CN108610352B (en) | 2020-08-04 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113121569A (en) * | 2021-04-20 | 2021-07-16 | 海南通用三洋药业有限公司 | Preparation method of mezlocillin sodium |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101570543A (en) * | 2009-06-04 | 2009-11-04 | 浙江工业大学 | Preparation method of mezlocillin sodium solvent crystal |
| CN101654457A (en) * | 2009-08-07 | 2010-02-24 | 菏泽睿鹰制药集团有限公司 | Method for synthesizing mezlocillin sodium through solvent method |
| CN102161666A (en) * | 2011-04-08 | 2011-08-24 | 苏州二叶制药有限公司 | Preparation method of mezlocillin sodium and mezlocillin sodium for injection |
-
2018
- 2018-06-12 CN CN201810603658.XA patent/CN108610352B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101570543A (en) * | 2009-06-04 | 2009-11-04 | 浙江工业大学 | Preparation method of mezlocillin sodium solvent crystal |
| CN101654457A (en) * | 2009-08-07 | 2010-02-24 | 菏泽睿鹰制药集团有限公司 | Method for synthesizing mezlocillin sodium through solvent method |
| CN102161666A (en) * | 2011-04-08 | 2011-08-24 | 苏州二叶制药有限公司 | Preparation method of mezlocillin sodium and mezlocillin sodium for injection |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113121569A (en) * | 2021-04-20 | 2021-07-16 | 海南通用三洋药业有限公司 | Preparation method of mezlocillin sodium |
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