CN103724386A - Preparation method of cortisone acetate - Google Patents
Preparation method of cortisone acetate Download PDFInfo
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- CN103724386A CN103724386A CN201310576848.4A CN201310576848A CN103724386A CN 103724386 A CN103724386 A CN 103724386A CN 201310576848 A CN201310576848 A CN 201310576848A CN 103724386 A CN103724386 A CN 103724386A
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- cortisone acetate
- hydrocortisone
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- acetylization
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- ITRJWOMZKQRYTA-RFZYENFJSA-N Cortisone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)CC2=O ITRJWOMZKQRYTA-RFZYENFJSA-N 0.000 title claims abstract description 41
- 229960003290 cortisone acetate Drugs 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims abstract description 68
- 229960000890 hydrocortisone Drugs 0.000 claims abstract description 32
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 24
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000003054 catalyst Substances 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 66
- 230000001590 oxidative effect Effects 0.000 claims description 29
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims description 22
- 230000003647 oxidation Effects 0.000 claims description 19
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 18
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 239000012295 chemical reaction liquid Substances 0.000 claims description 12
- 239000012043 crude product Substances 0.000 claims description 12
- 238000009413 insulation Methods 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 235000019439 ethyl acetate Nutrition 0.000 claims description 8
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 claims description 8
- 239000012046 mixed solvent Substances 0.000 claims description 8
- 239000007844 bleaching agent Substances 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 229960000583 acetic acid Drugs 0.000 claims description 6
- 239000012362 glacial acetic acid Substances 0.000 claims description 6
- 239000002994 raw material Substances 0.000 claims description 6
- 238000007670 refining Methods 0.000 claims description 6
- 229910001513 alkali metal bromide Inorganic materials 0.000 claims description 4
- ITHZDDVSAWDQPZ-UHFFFAOYSA-L barium acetate Chemical compound [Ba+2].CC([O-])=O.CC([O-])=O ITHZDDVSAWDQPZ-UHFFFAOYSA-L 0.000 claims description 4
- 238000007599 discharging Methods 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- SFDZPIDEIFZWQV-UHFFFAOYSA-N acetic acid;barium Chemical compound [Ba].CC(O)=O SFDZPIDEIFZWQV-UHFFFAOYSA-N 0.000 claims description 2
- 229960001067 hydrocortisone acetate Drugs 0.000 claims description 2
- 238000012545 processing Methods 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 10
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 abstract description 8
- 229910001430 chromium ion Inorganic materials 0.000 abstract description 3
- 239000007800 oxidant agent Substances 0.000 abstract description 3
- 230000001988 toxicity Effects 0.000 abstract description 2
- 231100000419 toxicity Toxicity 0.000 abstract description 2
- 239000002351 wastewater Substances 0.000 abstract description 2
- 239000005708 Sodium hypochlorite Substances 0.000 abstract 1
- 230000021736 acetylation Effects 0.000 abstract 1
- 238000006640 acetylation reaction Methods 0.000 abstract 1
- 231100001261 hazardous Toxicity 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000003999 initiator Substances 0.000 abstract 1
- 239000006227 byproduct Substances 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 239000011651 chromium Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 229910019093 NaOCl Inorganic materials 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 230000003637 steroidlike Effects 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000003444 phase transfer catalyst Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 208000017515 adrenocortical insufficiency Diseases 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 150000001886 cortisols Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229910001882 dioxygen Inorganic materials 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229960002163 hydrogen peroxide Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- CNFDGXZLMLFIJV-UHFFFAOYSA-L manganese(II) chloride tetrahydrate Chemical compound O.O.O.O.[Cl-].[Cl-].[Mn+2] CNFDGXZLMLFIJV-UHFFFAOYSA-L 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
Landscapes
- Steroid Compounds (AREA)
Abstract
The invention discloses a preparation method of cortisone acetate. According to the method, hydrocortisone is taken as an initiator, and preparation is performed through steps including acetylation, oxidization and the like. Sodium hypochlorite which is low in cost and environment-friendly is used for replacing chromic anhydride which is high in cost and larger in toxicity and serves as an oxidizing agent in an oxidation reaction, and a catalyst which cannot be recovered and recycled is not required in an oxidation reaction process. The preparation method of the cortisone acetate has the advantages that the production cost is reduced, the production operation is simplified, environmentally hazardous chromium ion wastewater is not discharged, and the method is suitable for industrial production.
Description
Technical field
The present invention relates to steroid drugs preparing technical field, particularly relate to a kind of preparation method of cortisone acetate.
Background technology
Cortisone acetate is adrenal cortex hormones drug, is mainly used in treating primary or secondary hypocortisolism disease, can alleviate body tissue and damaging be stimulated to the pathologic reaction producing.Cortisone acetate can also be as important intermediate, and for the production of steroid drugss such as hydrocortisone, methyl meticortelones, market outlook are boundless.
In < < whole nation bulk drug technique compilation > > (medicine management general bureau of country, one nine eight zero years), introduced the preparation technology of cortisone acetate.Wherein preparation technology take table hydrocortisone be a starting raw material, through over-churning, oxidation obtain cortisone acetate, this technique is 70% to the quality total recovery of stock chart hydrocortisone.Table hydrocortisone is fermentation byproduct in hydrocortisone production process, and its output accounts for 20% of hydrocortisone total amount, and this by product must just can fully utilize through products such as further structure of modification generation cortisone acetate, hydrocortisones in a large number.Domestic most manufacturer take and shows hydrocortisone and carry out cortisone acetate production as raw material.Chemical equation is as follows:
In above-mentioned traditional processing technology, oxidation operation be take chromic anhydride and is realized as oxygenant, Manganous chloride tetrahydrate as oxidation retarder.Because the strong oxidizing property of chromic anhydride can be further to the △ in compound structure
4(5)two keys and 17 Alpha-hydroxies be oxidized and produce steroid nucleus fracture by product, although take to reduce temperature of reaction in oxidizing reaction, use the measures such as oxidation retarder also cannot avoid the generation of by product, cause yield on the low side and quality product is had a negative impact; In the trade effluent producing at oxidation operation, contain a large amount of Cr
6+and Cr
3+, Cr wherein
6+for highly toxic substance, once reach some amount in this composition absorption human body, can cause cancer.These chromium ion harm environment, produce and bring very large environmental protection pressure to enterprise.
In recent years, with molecular oxygen O
2, oxydol H
2o
2deng the oxidation process for cleanly preparing of Green Oxidant, progressively cause people's attention, utilized the conventional oxidation agent such as Green Oxidant substitute chromium reagent, manganese reagent and high price iodine reagent to become the development trend in oxidizing reaction field.Because these oxygenants have conventional oxidation agent incomparable be cheaply easy to get, oxidized byproduct only has water, do not produce the advantages such as pollutent.But at application O
2and H
2o
2during as oxygenant, often need to use noble metal catalyst etc., because catalyzer is expensive and can not reclaim, reuse, these factors have objectively limited O simultaneously
2and H
2o
2widespread use in the suitability for industrialized production of oxidation field; < < chemical progress > > 2007, in (19) 11, introduced and utilized 2,2,6, the progress that 6-tetramethyl piperidine-N-oxyradical (TEMPO) and derivative thereof carry out alcohol oxidation: use TEMPO/NaBr/NaOCl system can realize the alcohol oxidation reaction of highly selective, TEMPO catalyzed oxidation is conventionally under TEMPO, NaBr and NaOCl existence, at pH=9,0-15 ℃ and CH
2cl
2for carrying out under the condition of solvent.Although the advantages such as that this method for oxidation has is simple to operate, reaction conditions is gentle, also exist expensive TEMPO to be difficult to reclaim, be difficult to the distinct disadvantage such as recycling.In addition, TEMPO catalyzed oxidation also faces following difficulty carrying out steroidal compounds alcohol oxidation application aspect: steroidal compounds has hydrophobicity conventionally, need to be dissolved in fat-soluble stronger organic solvent, and NaBr and NaOCl are insoluble in fat-soluble stronger organic solvent.In order to make oxidizing reaction smooth, need in reaction system, add phase-transfer catalyst.These limiting factors are unfavorable for realizing the application of TEMPO catalyzed oxidation aspect steroidal compounds suitability for industrialized production.
Summary of the invention
The preparation method who the object of this invention is to provide a kind of cortisone acetate, the above-mentioned defect existing to overcome prior art.
Preparation method of the present invention, its concrete steps are as follows:
Acetylization reaction: take and show hydrocortisone as raw material, obtain the solution (acetylization reaction liquid) of compound table hydrocortisone acetic ester by a step acetylization reaction;
Oxidizing reaction: after acetylization reaction is complete, middle body surface hydrocortisone acetic ester is separated without discharging, in acetylization reaction liquid, by oxidation step, react and obtain cortisone acetate crude product, then cortisone acetate crude product decolorizing and refining is obtained to cortisone acetate fine work;
In the preparation method of a kind of cortisone acetate of the present invention, acetylization reaction and prior art are basic identical, it is characterized in that oxidizing reaction specifically comprises the following steps:
Oxidizing reaction: after acetylization reaction is complete; middle body surface hydrocortisone acetic ester is separated without discharging; in acetylization reaction liquid directly and hypochlorite, alkali metal bromide generation oxidizing reaction obtain cortisone acetate crude product, then cortisone acetate crude product be added to decolorizing and refining in mixed solvent methyl alcohol-methylene dichloride obtain cortisone acetate fine work.
In above-mentioned oxidizing reaction, the good technology of preparing scheme of acetylization reaction liquid used is:
Acetylization reaction: take and show hydrocortisone as raw material, make solvent at Glacial acetic acid, under the existence of catalyst acetic acid barium, obtain the solution of compound table hydrocortisone acetic ester with aceticanhydride generation acetylization reaction.
Preparation method of the present invention further illustrates as follows:
The weightmeasurement ratio of showing hydrocortisone and Glacial acetic acid in acetylization reaction is 1:4～6; The weightmeasurement ratio of table hydrocortisone and aceticanhydride is 1:0.7～2; The weight ratio of table hydrocortisone and barium acetate is 1:0.18～0.28; Acetylization reaction insulation reaction temperature is 20 ℃～35 ℃, and the acetylization reaction insulation reaction time is 6～8 hours.
In oxidizing reaction, hypochlorite used is the chlorine bleach liquor in available chlorine, clorox content >=8.0%; Alkali metal bromide used is Sodium Bromide; Table hydrocortisone is 1:2～4 with take chlorine bleach liquor's the weightmeasurement ratio of available chlorine, clorox content >=8.0%; The weight ratio of table hydrocortisone and Sodium Bromide is 1:0.02～0.04; Oxidizing reaction temperature is 5 ℃～35 ℃, preferably 10 ℃～15 ℃; Oxidation time is 1～8 hour, preferably 3～4 hours; In mixed solvent methyl alcohol-methylene dichloride, the volume ratio of methyl alcohol and methylene dichloride is 1:0.8～1.7; The weightmeasurement ratio of table hydrocortisone and mixed solvent methyl alcohol-methylene dichloride is 12～16.
For simplicity, in the present invention, the proportioning of solid and liquid often recently represents with bulking value, and if no special instructions, this weightmeasurement ratio refers to the ratio of the weight of solid and the volume of liquid, that is, 1:1 refers to that 1g solid is than 1ml liquid.
Compared with prior art, the present invention has the following advantages:
1. in oxidizing reaction, use cheap, eco-friendly clorox to substitute chromic anhydride expensive, that toxicity is larger as oxygenant, not only reduced production cost, reduced reaction impurities, and avoided a large amount of chromium ion waste water of emission hazard environment;
2. oxidizing reaction is directly carried out between upper step acetylization reaction liquid and chlorine bleach liquor, Sodium Bromide, and the solvent system that has utilized more fully acetylization reaction liquid is to reaction substrate and clorox, Sodium Bromide good solubility energy.In oxidation reaction process, do not need to add TEMPO catalyzer expensive, that cannot reclaim, cannot reuse, do not need to add in addition phase-transfer catalyst yet, thereby simplified production operation, further reduced production cost, be suitable for suitability for industrialized production;
3. quality total recovery of the present invention reaches more than 88%, higher more than 18 percentage points than prior art yield (70%); The product content that the inventive method obtains reaches more than 99.0%, meets the quality standard of Chinese Pharmacopoeia (content 97.0%～103.0%).
Embodiment
With example, the present invention is illustrated below, these examples are intended to help to understand technique means of the present invention.But should be understood that these embodiment are exemplary, the present invention is not limited thereto.
Embodiment mono-
Acetylization reaction: add 20g table hydrocortisone, 5.6g barium acetate, 120ml Glacial acetic acid successively in reaction flask, stir 0.5 hour in 20 ℃.Then be cooled to 15 ℃, drip 14ml aceticanhydride.Dropwise, in 25 ℃～30 ℃ insulation reaction 8 hours.
Oxidizing reaction: the acetylization reaction liquid that above-mentioned insulation reaction is finished is cooled to 10 ℃, drips 0.8g Sodium Bromide and is dissolved in 80ml in the chlorine bleach liquor's of available chlorine, clorox content >=8.0% solution.Finish, in 13 ℃～15 ℃ insulation reaction 3 hours.Reaction solution is slowly added in the 1600ml frozen water that is chilled in advance 0 ℃～5 ℃, finish, continue at 0 ℃～5 ℃ and stir 0.5 hour, suction filtration, washing is neutral, drains to obtain cortisone acetate crude product.Cortisone acetate crude product is added in the mixed solvent being formed by 160ml methyl alcohol and 140ml methylene dichloride again, through decolorizing and refining, obtains 17.7g cortisone acetate fine work, content 99.5%.
Embodiment bis-
Acetylization reaction: add 20g table hydrocortisone, 3.6g barium acetate, 80ml Glacial acetic acid successively in reaction flask, stir 0.5 hour in 20 ℃.Then be cooled to 15 ℃, drip 40ml aceticanhydride.Dropwise, in 25 ℃～30 ℃ insulation reaction 6 hours.
Oxidizing reaction: the acetylization reaction liquid that above-mentioned insulation reaction is finished is cooled to 10 ℃, drips 0.4g Sodium Bromide and is dissolved in 40ml in the chlorine bleach liquor's of available chlorine, clorox content >=8.0% solution.Finish, in 13 ℃～15 ℃ insulation reaction 4 hours.Reaction solution is slowly added in the 1600ml frozen water that is chilled in advance 0 ℃～5 ℃, finish, continue at 0 ℃～5 ℃ and stir 0.5 hour, suction filtration, washing is neutral, drains to obtain cortisone acetate crude product.Cortisone acetate crude product is added in the mixed solvent being formed by 100ml methyl alcohol and 160ml methylene dichloride again, through decolorizing and refining, obtains 17.8g cortisone acetate fine work, content 99.3%.
Claims (10)
1. a preparation method for cortisone acetate, its processing step is:
Acetylization reaction: take and show hydrocortisone as raw material, obtain the solution (acetylization reaction liquid) of compound table hydrocortisone acetic ester by a step acetylization reaction;
Oxidizing reaction: after acetylization reaction is complete, middle body surface hydrocortisone acetic ester is separated without discharging, in acetylization reaction liquid, by oxidation step, react and obtain cortisone acetate crude product, then cortisone acetate crude product decolorizing and refining is obtained to cortisone acetate fine work;
It is characterized in that oxidizing reaction specifically comprises the following steps:
Oxidizing reaction: after acetylization reaction is complete; middle body surface hydrocortisone acetic ester is separated without discharging; in acetylization reaction liquid directly and hypochlorite, alkali metal bromide generation oxidizing reaction obtain cortisone acetate crude product, then cortisone acetate crude product be added to decolorizing and refining in mixed solvent methyl alcohol-methylene dichloride obtain cortisone acetate fine work.
2. the preparation method of a kind of cortisone acetate according to claim 1, is characterized in that: the hypochlorite described in oxidizing reaction is the chlorine bleach liquor in available chlorine, clorox content >=8.0%.
3. the preparation method of a kind of cortisone acetate according to claim 1, is characterized in that: the alkali metal bromide described in oxidizing reaction is Sodium Bromide.
4. the preparation method of a kind of cortisone acetate according to claim 1 and 2, is characterized in that: in oxidizing reaction, showing hydrocortisone is 1:2～4 with take chlorine bleach liquor's the weightmeasurement ratio of available chlorine, clorox content >=8.0%.
5. according to the preparation method of a kind of cortisone acetate described in claim 1 or 3, it is characterized in that: the weight ratio of showing hydrocortisone and Sodium Bromide in oxidizing reaction is 1:0.02～0.04.
6. the preparation method of a kind of cortisone acetate according to claim 1, is characterized in that: oxidizing reaction temperature is 5 ℃～35 ℃, preferably 10 ℃～15 ℃; Oxidation time is 1～8 hour, preferably 3～4 hours.
7. the preparation method of a kind of cortisone acetate according to claim 1, is characterized in that: in the mixed solvent methyl alcohol-methylene dichloride described in oxidizing reaction, the volume ratio of methyl alcohol and methylene dichloride is 1:0.8～1.7.
8. according to the preparation method of a kind of cortisone acetate described in claim 1 or 7, it is characterized in that: the weightmeasurement ratio of showing hydrocortisone and mixed solvent methyl alcohol-methylene dichloride in oxidizing reaction is 12～16.
9. the preparation method of a kind of cortisone acetate according to claim 1, is characterized in that: the acetylization reaction liquid described in oxidizing reaction obtains by acetylization reaction, and acetylization reaction specifically comprises the following steps:
Acetylization reaction: take and show hydrocortisone as raw material, make solvent at Glacial acetic acid, under the existence of catalyst acetic acid barium, obtain the solution of compound table hydrocortisone acetic ester with aceticanhydride generation acetylization reaction;
Wherein, the weightmeasurement ratio of table hydrocortisone and Glacial acetic acid is 1:4～6; The weightmeasurement ratio of table hydrocortisone and aceticanhydride is 1:0.7～2; The weight ratio of table hydrocortisone and barium acetate is 1:0.18～0.28.
10. according to the preparation method of a kind of cortisone acetate described in claim 1 or 9, it is characterized in that: acetylization reaction insulation reaction temperature is 20 ℃～35 ℃, and the acetylization reaction insulation reaction time is 6～8 hours.
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| CN201310576848.4A CN103724386A (en) | 2013-11-19 | 2013-11-19 | Preparation method of cortisone acetate |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104356187A (en) * | 2014-10-23 | 2015-02-18 | 华中药业股份有限公司 | Method for recycling hydrocortisone in hydrocortisone butyrate mother liquor |
| CN104610407A (en) * | 2015-01-27 | 2015-05-13 | 湖南新合新生物医药有限公司 | Refining method for hydrocortisone acetate |
| CN104761607A (en) * | 2015-03-17 | 2015-07-08 | 河南利华制药有限公司 | Preparation of prednisolone acetate |
| CN112279767A (en) * | 2020-10-29 | 2021-01-29 | 陕西嘉禾生物科技股份有限公司 | Preparation method of diacerein |
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| US2861088A (en) * | 1952-04-10 | 1958-11-18 | Upjohn Co | 11alpha, 17alpha, 21-trihydroxy-4-pregnene-3, 20-dione and esters thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104356187A (en) * | 2014-10-23 | 2015-02-18 | 华中药业股份有限公司 | Method for recycling hydrocortisone in hydrocortisone butyrate mother liquor |
| CN104610407A (en) * | 2015-01-27 | 2015-05-13 | 湖南新合新生物医药有限公司 | Refining method for hydrocortisone acetate |
| CN104761607A (en) * | 2015-03-17 | 2015-07-08 | 河南利华制药有限公司 | Preparation of prednisolone acetate |
| CN112279767A (en) * | 2020-10-29 | 2021-01-29 | 陕西嘉禾生物科技股份有限公司 | Preparation method of diacerein |
| CN112279767B (en) * | 2020-10-29 | 2023-02-03 | 陕西嘉禾生物科技股份有限公司 | Preparation method of diacerein |
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Application publication date: 20140416 |