CN106220479A - A kind of method recycling Sevoflurane impurity F (1) - Google Patents
A kind of method recycling Sevoflurane impurity F (1) Download PDFInfo
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- CN106220479A CN106220479A CN201610630384.4A CN201610630384A CN106220479A CN 106220479 A CN106220479 A CN 106220479A CN 201610630384 A CN201610630384 A CN 201610630384A CN 106220479 A CN106220479 A CN 106220479A
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- sevoflurane
- impurity
- environmental pollution
- recycles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/28—Preparation of ethers by reactions not forming ether-oxygen bonds from acetals, e.g. by dealcoholysis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/34—Separation; Purification; Stabilisation; Use of additives
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- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of recycling by Sevoflurane impurity F (1) in Sevoflurane crude product and reduce environmental pollution method.The fluorine-containing waste liquid being difficult to degrade in natural environment is converted into useful reagent by the method, decreases environmental pollution, reduces cost, it is achieved that the cleaning of Sevoflurane produces.
Description
Technical field
The present invention relates to organic chemistry and medicinal chemistry art, be specifically related to reclaim hexafluoro from Sevoflurane synthesis waste liquid different
The method of propyl chloride methyl ether.
Background technology
Sevoflurane is a kind of novel inhalation anesthetic, has quickly losing consciousness property and with the most restorative this is
The present age narcotic ideal characterisitics, and the convenience induced due to its face shield and reliable cardiovascular safety and side effect
Little, the advantage such as do not cause allergic reaction, and is widely used the most abroad.
Disclosed in the synthetic route predominantly United States Patent (USP) 6,100,434 reported at present prepared by a kind of method of novelty
Sevoflurane.With hexafluoroisopropanol as initiation material, through chloromethylation, prepare hexafluoro isopropyl chloromethylether, then with fluorine
Change potassium and carry out fluorination reaction, after rectification and purification, obtain Sevoflurane.This reaction scheme is short, and conversion ratio is high, is also current Sevoflurane master
The Industrialized synthesis method wanted.
But this method exists following technical barrier: during preparing key intermediate hexafluoro isopropyl chloromethylether, produce
Raw Sevoflurane impurity F (1), is ultimately introduced in Sevoflurane crude product, content about about 5%.Crude product is this material after rectification and purification
Being enriched in rectification residual solution, content is up to about 92%.This material is difficult to degrade in natural environment, how to recycle
Reducing environmental pollution is the industrialized difficult problem of puzzle.
Summary of the invention
It is an object of the invention to provide a kind of recycling by Sevoflurane impurity F (1) in Sevoflurane crude product and reduce ring
Environment pollution method.
The present invention is to realize above-mentioned purpose by the following method: use aluminum chloride, formaldehyde and Sevoflurane impurity F (1)
Reaction, is translated into the key intermediate hexafluoro isopropyl chloromethylether of Sevoflurane and is used.Specifically comprise the following steps that
In Sevoflurane rectification residual solution (containing 1), add aluminum chloride, temperature control-10 DEG C～20 DEG C, add first while stirring
Aldehyde (2) finishes continuation stirring, then drips hydrochloric acid, stratification after dropping, organic layer alkali liquid washing, stratification,
Collected organic layer obtains (3):
Preferably, the ratio of the amount of the material of described 1 and 2 is 1:(0.4-4)；
Described 1 is 1:(2-5 with the ratio of the amount of aluminum chloride material)；
Described reaction temperature controls at-5 DEG C～15 DEG C；
The described response time is 0.5-12 hour；
The concentration of described hydrochloric acid is 0.5-6mol/L；More preferably 3-6mol/L；1 with hydrochloric acid amount ratio be 1:
(0.5-4)(w/w)；
Described alkali one in sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate
Or it is multiple；
The concentration of described alkali is 0.5-6mol/L；More preferably 3-6mol/L；1 is 1 with the amount ratio of alkali:
(0.5-4)(w/w)；
The fluorine-containing waste liquid being difficult to degrade in natural environment is converted into useful reagent by the present invention, decreases environmental pollution,
Reduce cost, it is achieved that the cleaning of Sevoflurane produces.
Detailed description of the invention
Now further describe beneficial effects of the present invention by following example, do not illustrate part and be existing skill
Art, embodiment is only used for the purpose of illustration, does not limits the scope of the invention, and those of ordinary skill in the art are according to the present invention simultaneously
Within the obvious change made and modification are also contained in the scope of the invention.
Embodiment 1
Equipped with in thermometer, the constant pressure funnel there-necked flask with condensing tube, add Sevoflurane rectification residual solution
109.2g (containing 1 91.6%), aluminum chloride 80g, after mechanical agitation is cooled to 5 DEG C, being slowly added to mass fraction while stirring is
The formalin (altogether containing formaldehyde (2) 30g) of 50%, adds complete continuation and stirs reaction 3h, be then slowly added dropwise 3mol/L hydrochloric acid
Solution 100ml, stratification, organic layer 3mol/L sodium hydroxide solution 100ml washs, and water washs, and stratification, collection has
Machine layer obtains (3), and purity is 93.2%, and mass yield is 88.9%.
Embodiment 2
Equipped with in thermometer, the constant pressure funnel there-necked flask with condensing tube, add Sevoflurane rectification residual solution
105.1g (containing 1 95.1%), aluminum chloride 100g, after mechanical agitation is cooled to 5 DEG C, be slowly added to mass fraction while stirring
It is the formalin (altogether containing formaldehyde (2) 45g) of 50%, adds complete continuation and stir reaction 6h, be then slowly added dropwise 3mol/L salt
Acid solution 150ml, stratification, organic layer 3mol/L sodium hydroxide solution 150ml washs, and water washs, stratification, collects
Organic layer obtains (3), and purity is 89.2%, mass yield 89.5%.
Embodiment 3
Equipped with in thermometer, the constant pressure funnel there-necked flask with condensing tube, add Sevoflurane rectification residual solution
116.8g (containing 1 85.6%), aluminum chloride 80g, after mechanical agitation is cooled to-5 DEG C, be slowly added to mass fraction while stirring
It is the formalin (altogether containing formaldehyde (2) 12g) of 50%, adds complete continuation and stir reaction 10h, be then slowly added dropwise 3mol/L salt
Acid solution 100ml, stratification, organic layer 3mol/L sodium hydroxide solution 100ml washs, and water washs, stratification, collects
Organic layer obtains (3), and purity is 88.9%, mass yield 83.7%.
Embodiment 4
Equipped with in thermometer, the constant pressure funnel there-necked flask with condensing tube, add Sevoflurane rectification residual solution
124.2g (containing 1 80.5%), aluminum chloride 100g, after mechanical agitation is cooled to 15 DEG C, be slowly added to mass fraction while stirring
It is the formalin (altogether containing formaldehyde (2) 30g) of 50%, adds complete continuation and stir reaction 3h, be then slowly added dropwise 4mol/L salt
Acid solution 50ml, drips complete, stratification, and organic layer 4mol/L sodium hydroxide solution 50ml washs, and water washs, and stands and divides
Layer, collected organic layer obtains (3), and purity is 90.1%, mass yield 87.9%.
Embodiment 5
Equipped with in thermometer, the constant pressure funnel there-necked flask with condensing tube, add Sevoflurane rectification residual solution
110.9g (containing 1 90.2%), aluminum chloride 120g, mechanical agitation is cooled to 20 DEG C, is slowly added to mass fraction while stirring and is
The formalin (altogether containing formaldehyde (2) 45g) of 44%, adds complete continuation and stirs reaction 2h, be then slowly added dropwise 0.5mol/L salt
Acid solution 200ml, stratification, organic layer 0.5mol/L sodium hydroxide solution 200ml washs, and water washs, stratification, receives
Collection organic layer obtains (3), and purity is 84.6%, and yield is 81.9%.
Embodiment 6
Equipped with in thermometer, the constant pressure funnel there-necked flask with condensing tube, add Sevoflurane rectification residual solution
110.9g (containing 1 90.2%), aluminum chloride 160g, mechanical agitation is cooled to 0 DEG C, is slowly added to mass fraction while stirring and is
The formalin (altogether containing formaldehyde (2) 60g) of 50%, adds complete continuation and stirs reaction 6h, be then slowly added dropwise 4mol/L hydrochloric acid
Solution 60ml, drips complete, stratification, and organic layer 4mol/L sodium hydroxide solution 60ml washs, and water washs, and stands and divides
Layer, collected organic layer obtains (3), and purity is 85.3%, and yield is 83.0%.
Embodiment 7
Equipped with in thermometer, the constant pressure funnel there-necked flask with condensing tube, add Sevoflurane rectification residual solution
110.9g (containing 1 90.2%), aluminum chloride 120g, mechanical agitation is cooled to-10 DEG C, is slowly added to mass fraction while stirring
It is the formalin (altogether containing formaldehyde (2) 50g) of 50%, adds complete continuation and stir reaction 12h, be then slowly added dropwise 0.5mol/L
Hydrochloric acid solution 200ml, drips complete, stratification, and organic layer 0.5mol/L sodium hydroxide solution 200ml washs, and water washs,
Stratification, collected organic layer obtains (3), and purity is 50.7%, and yield is 49.9%.
Claims (10)
1. one kind recycles Sevoflurane impurity F (1), the method reducing environmental pollution, and its step is, uses aluminum chloride, first
Aldehyde reacts with Sevoflurane impurity F (1), be translated into the key intermediate hexafluoro isopropyl chloromethylether of Sevoflurane and add in order to
With.
2. a kind of Sevoflurane impurity F (1) that recycles as claimed in claim 1, the method for minimizing environmental pollution, its feature exists
In, specifically comprising the following steps that in Sevoflurane rectification residual solution (containing 1), add aluminum chloride, temperature control-10 DEG C～20 DEG C, limit is stirred
Limit adds formaldehyde (2), finishes continuation stirring, then drips hydrochloric acid, drip complete, stratification, and organic layer alkali liquid washing is quiet
Putting layering, collected organic layer obtains (3):
3. a kind of Sevoflurane impurity F (1) that recycles as claimed in claim 1, the method for minimizing environmental pollution, its feature exists
In, the ratio of the amount of 1 described and the material of 2 is 1:(0.4-4).
4. a kind of Sevoflurane impurity F (1) that recycles as claimed in claim 1, the method for minimizing environmental pollution, its feature exists
In, described 1 is 1:(2-5 with the ratio of the amount of aluminum chloride material).
5. a kind of Sevoflurane impurity F (1) that recycles as claimed in claim 1, the method for minimizing environmental pollution, its feature exists
In, described reaction temperature controls at-5 DEG C～15 DEG C.
6. a kind of Sevoflurane impurity F (1) that recycles as claimed in claim 1, the method for minimizing environmental pollution, its feature exists
In, the described response time is 0.5-12 hour.
7. a kind of Sevoflurane impurity F (1) that recycles as claimed in claim 1, the method for minimizing environmental pollution, its feature exists
In, the concentration of described hydrochloric acid is 0.5-6mol/L.
8. a kind of Sevoflurane impurity F (1) that recycles as claimed in claim 1, the method for minimizing environmental pollution, its feature exists
In, described 1 and hydrochloric acid amount ratio are 1:(0.5-4) (w/w).
9. a kind of Sevoflurane impurity F (1) that recycles as claimed in claim 1, the method for minimizing environmental pollution, its feature exists
In, described alkali one or many in sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate
Kind.
10. a kind of Sevoflurane impurity F (1) that recycles as claimed in claim 1, the method for minimizing environmental pollution, its feature
Being, the concentration of described alkali is 0.5-6mol/L.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610630384.4A CN106220479B (en) | 2016-08-03 | 2016-08-03 | A method of it recycles sevoflurane impurity F (1) |
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| CN201610630384.4A CN106220479B (en) | 2016-08-03 | 2016-08-03 | A method of it recycles sevoflurane impurity F (1) |
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| CN106220479B CN106220479B (en) | 2019-01-29 |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101381289A (en) * | 2008-10-14 | 2009-03-11 | 重庆福安药业有限公司 | Sevoflurane synthesizing method |
| CN101535231A (en) * | 2006-09-29 | 2009-09-16 | 克里斯泰利亚化学药物产品有限公司 | Process for the preparation of chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl) ethyl ether |
| EP2626341A1 (en) * | 2012-02-10 | 2013-08-14 | Solvay Sa | Manufacture of hexafluoroisopropanol |
-
2016
- 2016-08-03 CN CN201610630384.4A patent/CN106220479B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101535231A (en) * | 2006-09-29 | 2009-09-16 | 克里斯泰利亚化学药物产品有限公司 | Process for the preparation of chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl) ethyl ether |
| CN101381289A (en) * | 2008-10-14 | 2009-03-11 | 重庆福安药业有限公司 | Sevoflurane synthesizing method |
| EP2626341A1 (en) * | 2012-02-10 | 2013-08-14 | Solvay Sa | Manufacture of hexafluoroisopropanol |
Non-Patent Citations (1)
| Title |
|---|
| 李斌栋 等: "七氟醚的合成", 《中国医药工业杂志》 * |
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