CN115505062A - Preparation method of sevelamer carbonate - Google Patents
Preparation method of sevelamer carbonate Download PDFInfo
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- CN115505062A CN115505062A CN202211298636.XA CN202211298636A CN115505062A CN 115505062 A CN115505062 A CN 115505062A CN 202211298636 A CN202211298636 A CN 202211298636A CN 115505062 A CN115505062 A CN 115505062A
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- Prior art keywords
- stirring
- purified water
- sevelamer carbonate
- washing
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- PADGNZFOVSZIKZ-UHFFFAOYSA-N 2-(chloromethyl)oxirane;hydrogen carbonate;prop-2-enylazanium Chemical compound NCC=C.OC(O)=O.ClCC1CO1 PADGNZFOVSZIKZ-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 229960005441 sevelamer carbonate Drugs 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 19
- AIHIHVZYAAMDPM-UHFFFAOYSA-N oxiran-2-ylmethyl 3-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=CC(S(=O)(=O)OCC2OC2)=C1 AIHIHVZYAAMDPM-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000003756 stirring Methods 0.000 claims description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 33
- 239000008213 purified water Substances 0.000 claims description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- 238000006243 chemical reaction Methods 0.000 claims description 25
- 239000000243 solution Substances 0.000 claims description 22
- 238000001914 filtration Methods 0.000 claims description 20
- 239000012065 filter cake Substances 0.000 claims description 16
- 238000005406 washing Methods 0.000 claims description 15
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 14
- 239000007787 solid Substances 0.000 claims description 14
- 239000002351 wastewater Substances 0.000 claims description 14
- 238000001816 cooling Methods 0.000 claims description 13
- 239000000047 product Substances 0.000 claims description 12
- 229920002518 Polyallylamine hydrochloride Polymers 0.000 claims description 11
- 238000001035 drying Methods 0.000 claims description 11
- 229960003693 sevelamer Drugs 0.000 claims description 11
- ZNSIZMQNQCNRBW-UHFFFAOYSA-N sevelamer Chemical compound NCC=C.ClCC1CO1 ZNSIZMQNQCNRBW-UHFFFAOYSA-N 0.000 claims description 11
- 238000010438 heat treatment Methods 0.000 claims description 9
- 238000007664 blowing Methods 0.000 claims description 7
- 239000001569 carbon dioxide Substances 0.000 claims description 7
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 7
- 239000000725 suspension Substances 0.000 claims description 7
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 238000009987 spinning Methods 0.000 claims description 4
- 229910001220 stainless steel Inorganic materials 0.000 claims description 3
- 239000010935 stainless steel Substances 0.000 claims description 3
- -1 glycidyl m-nitrobenzenesulfonate Chemical compound 0.000 claims 1
- LRWZZZWJMFNZIK-UHFFFAOYSA-N 2-chloro-3-methyloxirane Chemical compound CC1OC1Cl LRWZZZWJMFNZIK-UHFFFAOYSA-N 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 231100000419 toxicity Toxicity 0.000 abstract description 3
- 230000001988 toxicity Effects 0.000 abstract description 3
- 238000003912 environmental pollution Methods 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 239000012535 impurity Substances 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 229920000642 polymer Polymers 0.000 description 3
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 2
- 230000007547 defect Effects 0.000 description 1
- 231100000024 genotoxic Toxicity 0.000 description 1
- 230000001738 genotoxic effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
- C08F8/44—Preparation of metal salts or ammonium salts
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- Chemical & Material Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of sevelamer carbonate. The toxicity of epoxy chloropropane in the traditional process is high, which is not beneficial to the safe production of the process, the invention uses m-nitrobenzenesulfonic acid glycidyl ester as a raw material, reduces impurities generated by epoxy chloropropane, and removes a large number of procedures of epoxy chloropropane; the process is more mild, efficient and stable. The preparation process of sevelamer carbonate provided by the invention has the advantages of simple process steps, simple operation steps, less environmental pollution, high product yield and purity, and can be used for industrial production.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of sevelamer carbonate.
Background
In the prior art, in the process for preparing sevelamer carbonate, a genotoxic substance epichlorohydrin is required. The toxicity of the epichlorohydrin in the process is high, and the process is not beneficial to safe production, so that a new preparation method of sevelamer carbonate is urgently needed to be developed.
Disclosure of Invention
The purpose of the invention is as follows: aiming at the defects in the prior art, the invention aims to provide a novel preparation method of sevelamer carbonate.
The technical scheme is as follows: the invention provides a preparation method of sevelamer carbonate, which is synthesized according to the following steps:
specifically, the method comprises the following steps: step 1) adding a polyallylamine hydrochloride aqueous solution and purified water into a reaction kettle, and adding m-nitrobenzenesulfonic acid glycidyl ester; cooling, and slowly pouring sodium hydroxide solution; heating and stirring for reaction; and after the reaction is finished, cooling, carrying out spin filtration, washing a filter cake, adding purified water, stirring, transferring the suspension into a D-level clean zone, stirring, washing, and carrying out spin filtration to obtain a white gelatinous solid, namely the sevelamer wet product.
And 2) adding the wet vemural product and purified water into a reaction kettle, uniformly stirring, introducing a proper amount of carbon dioxide at room temperature, stirring, performing filter spinning, drying a filter cake, and crushing to obtain a light yellow to off-white solid, namely the sevelamer carbonate.
Specifically, the temperature is reduced to 20 ℃, and the temperature is raised to 25-30 ℃ at first and then to 60 +/-2 ℃.
Specifically, the filter cake is washed by purified water with stirring until the conductivity of the wastewater solution is less than 20 mu s/cm.
Specifically, the suspension is transferred into a D-grade clean area to be stirred, washed and filtered for 1-2 times until the conductivity of the wastewater solution is less than 10 mu s/cm.
Specifically, the molar ratio of the polyallylamine hydrochloride to the m-nitrobenzenesulfonic acid glycidyl ester is 1:0.094 to 0.096; the molar ratio of polyallylamine hydrochloride to sodium hydroxide is 1:0.7 to 0.8.
Specifically, in step 2, the drying is: blowing and drying at 85-90 ℃ until the moisture is less than 2.0%.
Further, a typical scheme of the present invention is: step 1) adding a polyallylamine hydrochloride aqueous solution and purified water into a reaction kettle, and adding m-nitrobenzenesulfonic acid glycidyl ester; cooling to below 20 deg.C, and slowly adding sodium hydroxide solution; heating to 25-30 ℃, stirring and reacting for 1h; then heating to continue reacting for 3h; after the reaction is finished, cooling to below 20 ℃, and filtering by throwing. And stirring and washing the filter cake with a large amount of purified water until the conductivity of the wastewater solution is less than 20 mu s/cm, adding about 30kg/kg of purified water, stirring, washing the suspension in a D-level clean zone, and performing spin filtration for 1-2 times until the conductivity of the wastewater solution is less than 10 mu s/cm to obtain a white gelatinous solid, namely a sevelamer wet product.
And 2) adding the wet Veramel and purified water into a stainless steel reaction kettle, uniformly stirring, introducing a proper amount of carbon dioxide at room temperature, and stirring for 3 hours. Filtering, drying the filter cake by blowing at 85-90 ℃ until the water content is less than 2.0%, and crushing by using a universal crusher to obtain a light yellow to off-white solid, namely sevelamer carbonate.
Has the advantages that: the invention provides a preparation process of sevelamer, wherein toxicity of epoxy chloropropane in the original process is high, which is not beneficial to safe production of the process; the process is more mild, efficient and stable.
The preparation process of sevelamer carbonate provided by the invention has the advantages of simple process steps, simple operation steps, less environmental pollution, high product yield and purity, and can be used for industrial production.
Detailed Description
The following examples illustrate the invention in more detail, but the scope of the invention is not limited to the examples.
Example 1:
61.5g of polyallylamine hydrochloride aqueous solution (polymer content 49.24%) and 140g of purified water were put into a 500ml reaction flask, and 79.6g of m-nitrobenzenesulfonic acid glycidyl ester was added; cooling to below 20 ℃, and slowly pouring 28.9g of 32% sodium hydroxide solution; heating to 25-30 ℃, stirring and reacting for 1h. Then the temperature is increased to 60 +/-2 ℃ to continue the reaction for 3h. After the reaction is finished, cooling to below 20 ℃, and filtering by throwing. And (3) stirring and washing the filter cake by using a large amount of purified water until the conductivity of the wastewater solution is less than 20 mu s/cm, adding the purified water, stirring, centrifuging and filtering by throwing for 1-2 times until the conductivity of the wastewater solution is less than 10 mu s/cm, and obtaining white gelatinous solid, namely the sevelamer wet product.
Adding the wet sevelamer product obtained in the previous step and 150g of purified water into a 1000ml reaction bottle, uniformly stirring, introducing a proper amount of carbon dioxide at room temperature, and stirring for 3 hours. And (3) filtering in a throwing way, drying the filter cake by blowing at 85-90 ℃ until the water content is less than 2.0%, and crushing by using a universal crusher to obtain 28.9g of light yellow to off-white solid, namely sevelamer carbonate.
Example 2:
1230g of polyallylamine hydrochloride aqueous solution (polymer content 49.24%) and 2800g of purified water were put into a 20L reactor, and 1600g of m-nitrobenzenesulfonic acid glycidyl ester was added; cooling to below 20 ℃, and slowly pouring 620g of 30% sodium hydroxide solution; heating to 25-30 ℃, stirring and reacting for 1h. Then the temperature is increased to 60 +/-2 ℃ to continue the reaction for 3h. After the reaction is finished, cooling to below 20 ℃, and filtering by throwing. And (3) stirring and washing the filter cake by using a large amount of purified water until the conductivity of the wastewater solution is less than 20 mu s/cm, adding the purified water, stirring, centrifuging, and filtering by spinning until the conductivity of the wastewater solution is less than 10 mu s/cm to obtain a white gelatinous solid, namely the sevelamer wet product.
Adding the wet sevelamer product obtained in the previous step and 3000g of purified water into a 20L reaction kettle, uniformly stirring, introducing a proper amount of carbon dioxide at room temperature, and stirring for 3 hours. And (3) filtering by spinning, drying the filter cake by blowing at 85-90 ℃ until the water content is less than 2.0%, and crushing by using a universal crusher to obtain 301g of light yellow to off-white solid, namely sevelamer carbonate.
Example 3:
61.5kg of an aqueous polyallylamine hydrochloride solution (polymer content 49.24%) and 140.0kg of purified water were charged into a 500L glass-lined reactor, the temperature was reduced to 20 ℃ or below, and 29.0kg of a 32% sodium hydroxide solution was slowly poured in. Then the temperature is reduced to 0 +/-2 ℃, and 80.0kg of m-nitrobenzenesulfonic acid glycidyl ester is added. Stirring at 0 +/-2 deg.C for half an hour, heating to 25-30 deg.C, and stirring for reaction for 1 hr. Then the temperature is increased to 60 +/-2 ℃ to continue the reaction for 3 hours. After the reaction is finished, cooling to below 20 ℃, and filtering by throwing. And stirring and washing the filter cake with a large amount of purified water until the conductivity of the wastewater solution is less than 20 mu s/cm, adding the purified water, stirring, transferring the suspension into a D-grade clean zone, stirring and washing, and performing spin-filtration for 1-2 times until the conductivity of the wastewater solution is less than 10 mu s/cm to obtain a white gelatinous solid, namely the wet sevelamer product.
Adding a wet sevelamer and 150.0kg of purified water into a 1000L stainless steel reaction kettle, uniformly stirring, introducing a proper amount of carbon dioxide (120-150L/kg, the flow rate is about 15-20L/min) at room temperature, and stirring for 3 hours. Filtering, drying the filter cake by blowing at 85-90 ℃ until the water content is less than 2.0%, and crushing by using a universal crusher to obtain 30.4kg of light yellow to off-white solid, namely sevelamer carbonate.
The above description is only a preferred embodiment of the present application and is not intended to limit the present application.
Claims (8)
1. The preparation method of sevelamer carbonate is characterized by comprising the following steps:
2. the method for preparing sevelamer carbonate according to claim 1, comprising the steps of: step 1) adding a polyallylamine hydrochloride aqueous solution and purified water into a reaction kettle, and adding m-nitrobenzenesulfonic acid glycidyl ester; cooling, and slowly pouring sodium hydroxide solution; heating and stirring for reaction; after the reaction is finished, cooling, carrying out spin filtration, washing a filter cake, adding purified water, stirring, transferring the suspension into a D-level clean zone, stirring, washing and spin filtration to obtain a white gelatinous solid, namely a sevelamer wet product;
and 2) adding the wet vemural product and purified water into a reaction kettle, uniformly stirring, introducing a proper amount of carbon dioxide at room temperature, stirring, performing filter spinning, drying a filter cake, and crushing to obtain a light yellow to off-white solid, namely the sevelamer carbonate.
3. The method for preparing sevelamer carbonate according to claim 1, wherein the temperature is reduced to 20 ℃, and the temperature is increased to 25-30 ℃ at first and is increased to 60 ℃ ± 2 ℃.
4. The method for preparing sevelamer carbonate according to claim 1, wherein the washing step is carried out by washing the filter cake with purified water under stirring until the conductivity of the waste water solution is less than 20 μ s/cm.
5. The method for preparing sevelamer carbonate according to claim 1, wherein the suspension is transferred into a D-grade clean zone for stirring, washing and filtering for 1-2 times until the conductivity of the wastewater solution is less than 10 μ s/cm.
6. The method for preparing sevelamer carbonate according to claim 1, wherein the molar ratio of polyallylamine hydrochloride to glycidyl m-nitrobenzenesulfonate is 1:0.094 to 0.096; the molar ratio of polyallylamine hydrochloride to sodium hydroxide is 1:0.7 to 0.8.
7. The method for preparing sevelamer carbonate according to claim 1, wherein in step 2, the drying is: blowing and drying at 85-90 ℃ until the moisture is less than 2.0%.
8. The method for preparing sevelamer carbonate according to claim 1, wherein step 1) comprises adding an aqueous solution of polyallylamine hydrochloride and purified water to a reaction vessel, and adding m-nitrophenylsulfonic acid glycidyl ester; cooling to below 20 deg.C, and slowly adding sodium hydroxide solution; heating to 25-30 ℃, stirring and reacting for 1h; heating to continue reacting for 3h; after the reaction is finished, cooling to below 20 ℃, and filtering by throwing. Stirring and washing a filter cake by using a large amount of purified water until the conductivity of the wastewater solution is less than 20 mu s/cm, adding about 30kg/kg of purified water, stirring, washing the suspension in a D-grade clean area, and performing spin filtration for 1-2 times until the conductivity of the wastewater solution is less than 10 mu s/cm to obtain a white gelatinous solid, namely a sevelamer wet product;
and 2) adding the wet Veramel and purified water into a stainless steel reaction kettle, uniformly stirring, introducing a proper amount of carbon dioxide at room temperature, and stirring for 3 hours. Filtering, drying the filter cake by blowing at 85-90 ℃ until the water content is less than 2.0%, and crushing by using a universal crusher to obtain a light yellow to off-white solid, namely sevelamer carbonate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211298636.XA CN115505062A (en) | 2022-10-19 | 2022-10-19 | Preparation method of sevelamer carbonate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211298636.XA CN115505062A (en) | 2022-10-19 | 2022-10-19 | Preparation method of sevelamer carbonate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115505062A true CN115505062A (en) | 2022-12-23 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211298636.XA Withdrawn CN115505062A (en) | 2022-10-19 | 2022-10-19 | Preparation method of sevelamer carbonate |
Country Status (1)
| Country | Link |
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| CN (1) | CN115505062A (en) |
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2022
- 2022-10-19 CN CN202211298636.XA patent/CN115505062A/en not_active Withdrawn
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| Date | Code | Title | Description |
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| PB01 | Publication | ||
| PB01 | Publication | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20221223 |