CN105348359A - Preparation technology for dexamethasone sodium phosphate - Google Patents
Preparation technology for dexamethasone sodium phosphate Download PDFInfo
- Publication number
- CN105348359A CN105348359A CN201510758974.0A CN201510758974A CN105348359A CN 105348359 A CN105348359 A CN 105348359A CN 201510758974 A CN201510758974 A CN 201510758974A CN 105348359 A CN105348359 A CN 105348359A
- Authority
- CN
- China
- Prior art keywords
- dexamethasone
- reaction
- sodium phosphate
- preparation technology
- carried out
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a preparation technology for dexamethasone sodium phosphate. The preparation technology comprises the following steps: a ring-opening reaction is carried out, namely, dexamethasone acetate epoxide is employed as an initial raw material, HF and DMF are added, a reaction is performed for 3h, a ring-opening reaction is carried out and a dexamethasone acetate solution is prepared; recrystallization is carried out, namely, acetone or ether is added in the dexamethasone acetate solution, recrystallization is carried out, dexamethasone acetate is prepared, and rotary distillation is employed to remove the solvent after recrystallization; base catalysis hydrolysis is carried out, namely, dexamethasone acetate is added in Na2CO3 and methanol, a reaction is carried out for 10min, dexamethasone is prepared; pyrophosphoryl chlorine esterification is carried out, namely, dexamethasone is reacted with pyrophosphoryl chlorine and THF, and dexamethasone phosphate ester is prepared; a neutralization salt forming reaction is carried out, namely, the dexamethasone phosphate ester obtained from the fourth step is reacted with NaOH and methanol, and dexamethasone sodium phosphate is prepared. The steps are simple, raw materials are easily available, the reaction conditions are mild, the preparation technology is suitable for industrial production, and the cost is low.
Description
Technical field
The present invention relates to medical art, particularly, relate to a kind of preparation technology of dexamethasone sodium phosphate.
Background technology
Dexamethasone sodium phosphate, chemistry 16 Alpha-Methyl-11 β, 17 α by name, 21 trihydroxy--9 α-pregna-fluoride-Isosorbide-5-Nitrae-diene-3,20-diketone-21-organic phosphate disodium salt, be a kind of Aeroseb-Dex, there is anti-inflammatory, antianaphylaxis, rheumatism, immunosuppressive action.The mechanism of action is: (1) anti-inflammatory action: can alleviate and prevent tissue to the reaction of inflammation, thus the performance reduced inflammation.Can inflammation-inhibiting cell, comprise scavenger cell and white corpuscle gathering at inflammation part, and suppress phagolysis, the synthesis of lysosomal release and inflammation chemistry intermediary and release.(2) immunosuppressive action: comprise prevent or T suppression cell mediation immune response, the anaphylaxis of retardance, reduce the number of T lymphocyte, monocyte, eosinophil, reduce the binding ability of immunoglobulin (Ig) and cell surface receptor, and suppress synthesis and the release of interleukin, thus reduce T lymphocyte to lymphocyte transformation, and alleviate and formerly send out expansion immunoreactive.Also can reduce immunity and check thing by basilar membrane, and the concentration of complement component and immunoglobulin (Ig) can be reduced.
Dexamethasone sodium phosphate is mainly used in supersensitivity and auto-immune inflammatory disease, be used for connective tissue disease (CTD), reactivity rheumatosis, rheumatoid arthritis, lupus erythematosus, serious bronchial asthma, serious dermatitis, ulcerative colitis, acute leukemia etc., also for some severe infections and poisoning.The complex therapy of malignant lymphoma.Within 1 hour after intramuscular injection, blood peak concentration of drug can be reached, and its plasma protein binding ratio is low compared with other corticosteroids medicine, therefore clinical its injection liquid inhibitor conventional.
Preparation method's complex process of existing dexamethasone sodium phosphate and yield is low.
Summary of the invention
Technical problem to be solved by this invention is to provide the preparation technology of the dexamethasone sodium phosphate that a kind of technique is simple, yield is high.
The present invention's adopted technical scheme that solves the problem is: a kind of preparation technology of dexamethasone sodium phosphate, comprises the following steps:
1), ring-opening reaction: with dexamethasone acetate epoxy material for starting raw material, add HF, DMF, temperature of reaction is-10 DEG C ~ 0 DEG C, and reaction times 3h carries out ring-opening reaction and obtains dexamethasone acetate solution;
2), recrystallization: add acetone or ether and carry out recrystallization and obtain dexamethasone acetate in dexamethasone acetate solution, adopt after recrystallization to revolve and steam except desolventizing;
3), alkali catalyzed hydrolysis: by step 2) dexamethasone acetate that obtains joins Na
2cO
3with in methyl alcohol, temperature of reaction 20 DEG C ~ 30 DEG C, obtains dexamethasone after reaction times 10min;
4), pyrophosphoryl chloride esterification: dexamethasone step 3) obtained and pyrophosphoryl chloride, THF are obtained by reacting dexamethasone phosphate;
5), be neutralized into reactant salt: dexamethasone phosphate step 4) obtained and NaOH, methyl alcohol react, temperature of reaction 20 DEG C ~ 30 DEG C, the reaction times, 1h obtained dexamethasone sodium phosphate.
Reagent used in the present invention is available reagent, wherein HF is hydrofluoric acid, and DMF is dimethyl formamide, and the step that the present invention prepares dexamethasone sodium phosphate is simple, raw material is easy to get, reaction conditions is gentle, is suitable for suitability for industrialized production, and with low cost, and, the present invention adopts acetone to be used for the recrystallization of dexamethasone acetate, can effectively improve dexamethasone acetate recrystallization ratio, and then improves the yield of the finished product dexamethasone sodium phosphate.
Further, in step 1), the mol ratio of dexamethasone acetate epoxy material, HF, DMF is 1 ~ 2:92 ~ 95:44 ~ 50.
Further, dexamethasone acetate, Na in step 3)
2cO
3, methyl alcohol mol ratio be 1 ~ 2:4 ~ 8:214 ~ 220.
Further, in step 4), the mol ratio of dexamethasone, pyrophosphoryl chloride, THF is 1 ~ 3:5 ~ 8:19 ~ 25.
Further, in step 5), the mol ratio of dexamethasone phosphate, NaOH, methyl alcohol is 1 ~ 2:2 ~ 5:169 ~ 175.
To sum up, the invention has the beneficial effects as follows:
The step that the present invention prepares dexamethasone sodium phosphate is simple, raw material is easy to get, reaction conditions is gentle, be suitable for suitability for industrialized production, and with low cost, and the present invention adopts acetone to be used for the recrystallization of dexamethasone acetate, can effectively improve dexamethasone acetate recrystallization ratio, and then improve the yield of the finished product dexamethasone sodium phosphate.
Embodiment
Below in conjunction with embodiment, to the detailed description further of invention do, but embodiments of the present invention are not limited thereto.
Embodiment 1:
A preparation technology for dexamethasone sodium phosphate, comprises the following steps:
1), ring-opening reaction: with dexamethasone acetate epoxy material for starting raw material, add HF, DMF, temperature of reaction is-10 DEG C, and reaction times 3h carries out ring-opening reaction and obtains dexamethasone acetate solution, and the mol ratio of dexamethasone acetate epoxy material, HF, DMF is 1:92:44;
2), recrystallization: add acetone and carry out recrystallization and obtain dexamethasone acetate in dexamethasone acetate solution, adopt after recrystallization to revolve and steam except desolventizing;
3), alkali catalyzed hydrolysis: by step 2) dexamethasone acetate that obtains joins Na
2cO
3with in methyl alcohol, temperature of reaction 20 DEG C, obtains dexamethasone after reaction times 10min, dexamethasone acetate, Na
2cO
3, methyl alcohol mol ratio be 1:4:214;
4), pyrophosphoryl chloride esterification: dexamethasone step 3) obtained and pyrophosphoryl chloride, THF are obtained by reacting dexamethasone phosphate, and the mol ratio of dexamethasone, pyrophosphoryl chloride, THF is 1:5:19;
5), be neutralized into reactant salt: dexamethasone phosphate step 4) obtained and NaOH, methyl alcohol react, temperature of reaction 20 DEG C, and the reaction times, 1h obtained dexamethasone sodium phosphate, the mol ratio of dexamethasone phosphate, NaOH, methyl alcohol is 1:2:169.
Embodiment 2:
A preparation technology for dexamethasone sodium phosphate, comprises the following steps:
1), ring-opening reaction: with dexamethasone acetate epoxy material for starting raw material, add HF, DMF, temperature of reaction is-5 DEG C, and reaction times 3h carries out ring-opening reaction and obtains dexamethasone acetate solution, and the mol ratio of dexamethasone acetate epoxy material, HF, DMF is 1.5:94:48;
2), recrystallization: add acetone and carry out recrystallization and obtain dexamethasone acetate in dexamethasone acetate solution, adopt after recrystallization to revolve and steam except desolventizing;
3), alkali catalyzed hydrolysis: by step 2) dexamethasone acetate that obtains joins Na
2cO
3with in methyl alcohol, temperature of reaction 25 DEG C, obtains dexamethasone after reaction times 10min, dexamethasone acetate, Na
2cO
3, methyl alcohol mol ratio be 1.5:6:216;
4), pyrophosphoryl chloride esterification: dexamethasone step 3) obtained and pyrophosphoryl chloride, THF are obtained by reacting dexamethasone phosphate, and the mol ratio of dexamethasone, pyrophosphoryl chloride, THF is 2:6:22;
5), be neutralized into reactant salt: dexamethasone phosphate step 4) obtained and NaOH, methyl alcohol react, temperature of reaction 25 DEG C, and the reaction times, 1h obtained dexamethasone sodium phosphate, the mol ratio of dexamethasone phosphate, NaOH, methyl alcohol is 1.5:4:173.
Embodiment 3:
A preparation technology for dexamethasone sodium phosphate, comprises the following steps:
1), ring-opening reaction: with dexamethasone acetate epoxy material for starting raw material, add HF, DMF, temperature of reaction is 0 DEG C, and reaction times 3h carries out ring-opening reaction and obtains dexamethasone acetate solution, and the mol ratio of dexamethasone acetate epoxy material, HF, DMF is 2:95:50;
2), recrystallization: add ether and carry out recrystallization and obtain dexamethasone acetate in dexamethasone acetate solution, adopt after recrystallization to revolve and steam except desolventizing;
3), alkali catalyzed hydrolysis: by step 2) dexamethasone acetate that obtains joins Na
2cO
3with in methyl alcohol, temperature of reaction 30 DEG C, obtains dexamethasone after reaction times 10min, dexamethasone acetate, Na
2cO
3, methyl alcohol mol ratio be 2:8:220;
4), pyrophosphoryl chloride esterification: dexamethasone step 3) obtained and pyrophosphoryl chloride, THF are obtained by reacting dexamethasone phosphate, and the mol ratio of dexamethasone, pyrophosphoryl chloride, THF is 3:8:25;
5), be neutralized into reactant salt: dexamethasone phosphate step 4) obtained and NaOH, methyl alcohol react, temperature of reaction 30 DEG C, and the reaction times, 1h obtained dexamethasone sodium phosphate, the mol ratio of dexamethasone phosphate, NaOH, methyl alcohol is 2:5:175.
As mentioned above, the present invention can be realized preferably.
Claims (5)
1. a preparation technology for dexamethasone sodium phosphate, is characterized in that, comprises the following steps:
1), ring-opening reaction: with dexamethasone acetate epoxy material for starting raw material, add HF, DMF, temperature of reaction is-10 DEG C ~ 0 DEG C, and reaction times 3h carries out ring-opening reaction and obtains dexamethasone acetate solution;
2), recrystallization: add acetone or ether and carry out recrystallization and obtain dexamethasone acetate in dexamethasone acetate solution, adopt after recrystallization to revolve and steam except desolventizing;
3), alkali catalyzed hydrolysis: by step 2) dexamethasone acetate that obtains joins Na
2cO
3with in methyl alcohol, temperature of reaction 20 DEG C ~ 30 DEG C, obtains dexamethasone after reaction times 10min;
4), pyrophosphoryl chloride esterification: dexamethasone step 3) obtained and pyrophosphoryl chloride, THF are obtained by reacting dexamethasone phosphate;
5), be neutralized into reactant salt: dexamethasone phosphate step 4) obtained and NaOH, methyl alcohol react, temperature of reaction 20 DEG C ~ 30 DEG C, the reaction times, 1h obtained dexamethasone sodium phosphate.
2. the preparation technology of a kind of dexamethasone sodium phosphate according to claim 1, is characterized in that, in step 1), the mol ratio of dexamethasone acetate epoxy material, HF, DMF is 1 ~ 2:92 ~ 95:44 ~ 50.
3. the preparation technology of a kind of dexamethasone sodium phosphate according to claim 1, is characterized in that, dexamethasone acetate, Na in step 3)
2cO
3, methyl alcohol mol ratio be 1 ~ 2:4 ~ 8:214 ~ 220.
4. the preparation technology of a kind of dexamethasone sodium phosphate according to claim 1, is characterized in that, in step 4), the mol ratio of dexamethasone, pyrophosphoryl chloride, THF is 1 ~ 3:5 ~ 8:19 ~ 25.
5. the preparation technology of a kind of dexamethasone sodium phosphate according to claim 1, is characterized in that, in step 5), the mol ratio of dexamethasone phosphate, NaOH, methyl alcohol is 1 ~ 2:2 ~ 5:169 ~ 175.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510758974.0A CN105348359A (en) | 2015-11-10 | 2015-11-10 | Preparation technology for dexamethasone sodium phosphate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510758974.0A CN105348359A (en) | 2015-11-10 | 2015-11-10 | Preparation technology for dexamethasone sodium phosphate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105348359A true CN105348359A (en) | 2016-02-24 |
Family
ID=55324440
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510758974.0A Pending CN105348359A (en) | 2015-11-10 | 2015-11-10 | Preparation technology for dexamethasone sodium phosphate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105348359A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110964075A (en) * | 2018-09-30 | 2020-04-07 | 天津药业研究院有限公司 | Preparation method of betamethasone phosphate and sodium salt thereof |
-
2015
- 2015-11-10 CN CN201510758974.0A patent/CN105348359A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110964075A (en) * | 2018-09-30 | 2020-04-07 | 天津药业研究院有限公司 | Preparation method of betamethasone phosphate and sodium salt thereof |
| CN110964075B (en) * | 2018-09-30 | 2022-09-06 | 天津药业研究院股份有限公司 | Preparation method of betamethasone phosphate and sodium salt thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109880100B (en) | Preparation method of cage-type octaphenyl silsesquioxane | |
| CN104768908A (en) | Method for preparing high-purity anhydrosugar alcohol using sequential combination of thin film distillation and short path distillation | |
| CN103232369B (en) | Preparation method of fmoc chloride glutamic acid-5-tert-butyl ester | |
| CN105348359A (en) | Preparation technology for dexamethasone sodium phosphate | |
| CN105130798A (en) | Novel synthetic method for F-acrylic acid and derivative thereof | |
| CN105348358A (en) | Preparation method for dexamethasone sodium phosphate | |
| CN116393170B (en) | Preparation method of trifluoro methanesulfonic anhydride | |
| CN101070306A (en) | Synthesizing method for 1,3, dimethyl-2-imidazolidinone | |
| CN103601766B (en) | Fondaparinux sodium pentasaccharide intermediate and preparation method thereof | |
| CN105348360A (en) | Preparation technology for dexamethasone sodium phosphate based on raising recrystalline particle size | |
| CN103709209A (en) | Isopropyl-beta-D-thiogalactoside preparation method | |
| CN103421023B (en) | A kind of synthesis technique of CCI-779 | |
| CN103665063B (en) | A kind of method preparing isopropyl-β-D-thiogalactoside(IPTG) | |
| CN105342992A (en) | Preparation method of dexamethasone sodium phosphate injection | |
| CN103193845B (en) | Method for synthesizing intermediate of 17-hydroxy acylated cortical hormone steroid medicament | |
| CN105342991A (en) | Preparation technology of dexamethasone sodium phosphate injection for quality improvement | |
| CN105342993A (en) | Preparation technology of dexamethasone sodium phosphate injection | |
| CN105326787A (en) | Technology for preparing dexamethasone sodium phosphate injection | |
| CN104478715B (en) | The preparation method of compound | |
| CN103739545A (en) | Simple preparation method of vitamin B6 | |
| CN105326788A (en) | Preparation method of dexamethasone sodium phosphate for injection | |
| CN109180592B (en) | Synthesis method of 7-chloro-2- (3-chlorophenyl) quinazoline | |
| CN101987825B (en) | Method for preparing 2-amino-3-methyl-4-methoxy acetophenone | |
| CN105439978A (en) | Preparation method of acotiamide intermediate | |
| CN101845073B (en) | Preparation method and application of 1alpha-dehydroepiandrosterone |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20160224 |