CN101717428B - Method for synthesizing budesonide - Google Patents
Method for synthesizing budesonide Download PDFInfo
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- CN101717428B CN101717428B CN2009101550582A CN200910155058A CN101717428B CN 101717428 B CN101717428 B CN 101717428B CN 2009101550582 A CN2009101550582 A CN 2009101550582A CN 200910155058 A CN200910155058 A CN 200910155058A CN 101717428 B CN101717428 B CN 101717428B
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- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 title claims abstract description 40
- 229960004436 budesonide Drugs 0.000 title claims abstract description 34
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 16
- 238000000034 method Methods 0.000 title claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 5
- 239000007788 liquid Substances 0.000 claims description 40
- 150000002500 ions Chemical class 0.000 claims description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 30
- 230000002378 acidificating effect Effects 0.000 claims description 30
- -1 16 Alpha-hydroxy Prednisolone Acetates Chemical class 0.000 claims description 29
- 238000000605 extraction Methods 0.000 claims description 16
- 239000012044 organic layer Substances 0.000 claims description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 10
- 239000012153 distilled water Substances 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 4
- 229910016467 AlCl 4 Inorganic materials 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 239000002608 ionic liquid Substances 0.000 abstract description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 2
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 abstract 4
- 239000011831 acidic ionic liquid Substances 0.000 abstract 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 1
- 239000012295 chemical reaction liquid Substances 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- 125000000542 sulfonic acid group Chemical group 0.000 abstract 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 239000002994 raw material Substances 0.000 description 12
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000012046 mixed solvent Substances 0.000 description 6
- 229960002800 prednisolone acetate Drugs 0.000 description 6
- 239000012265 solid product Substances 0.000 description 6
- 230000009466 transformation Effects 0.000 description 6
- SEKYBDYVXDAYPY-ILNISADRSA-N (8s,9s,10r,11s,13s,14s,16r,17s)-11,16,17-trihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-3-one Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 SEKYBDYVXDAYPY-ILNISADRSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000012429 reaction media Substances 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000002815 homogeneous catalyst Substances 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- SAOSCTYRONNFTC-UHFFFAOYSA-N methyl-capric acid Natural products CCCCCCCCC(C)C(O)=O SAOSCTYRONNFTC-UHFFFAOYSA-N 0.000 description 2
- PRVLWKMLAPTNIR-UHFFFAOYSA-N 2-butyl-5-methyl-1h-imidazole Chemical class CCCCC1=NC=C(C)N1 PRVLWKMLAPTNIR-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 150000001449 anionic compounds Chemical class 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000005518 electrochemistry Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000002638 heterogeneous catalyst Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 150000002891 organic anions Chemical class 0.000 description 1
- 150000002892 organic cations Chemical class 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
The invention relates to a method for synthesizing budesonide, which comprises the following steps of: adding 16 alpha-hydroxy hydroprednisone shown in a formula (I) and n-butanal into acidic ionic liquid shown in a formula (II) to perform reaction for 1 to 10 hours at the temperature of between 10 and 100 DEG C; and after the reaction is finished, performing subsequent treatment on the reaction liquid to obtain the budesonide shown in a formula (III), wherein the quantity ratio of the 16 alpha-hydroxy hydroprednisone to the n-butanal is 1 to 2-5; the mass ratio of the 16 alpha-hydroxy hydroprednisone to the acidic ionic liquid is 1 to 1-10; and in the acidic ionic liquid, R is C1 to C10 alkyl or substituted alkyl, and the substituent group is sulfonic acid group or carboxyl, and L is HSO42-, COO-, BF4-, BF6-, AlCl4- or CF3SO3-. The method for synthesizing the budesonide has the advantages of easy operation, high capacity, good efficiency, little three wastes, convenient subsequent treatment and reusable ionic liquid, which is an economical and practical environmentally-friendly technique.
Description
(1) technical field
The present invention relates to a kind of synthesizing budesonide, particularly utilize acidic ion liquid, synthesize the method for budesonide as reaction medium and catalyzer.
(2) background technology
Budesonide, its English chemistry (11 β, 16 α)-16 by name, 17-[Butylidenebis (oxy)]-11,21-dihydroxypregna-1,4-diene-3,20-dione is a kind of corticosteroids medicine with very strong antiinflammation.Owing in similar drug, have higher part and systemic effect ratio, thereby be more suitable for local application, be to suck treatment asthma and sparge the anaphylactoid line medicine of nasal cavity therapy with aerosol.Final step is that 22 newly-generated carbon are racemic ethylidene ether structure with 16 Alpha-hydroxy Prednisolone Acetates and butyraldehyde-n reaction in the building-up reactions of budesonide.In recent years, we just are being devoted to all kinds of ion liquid synthetic and ion liquid applied researcies, and acidic ion liquid is used for the synthesis technique of hormone medicine as reaction medium and catalyzer, are economical and practical eco-friendly cleaner production new technologies.
Ionic liquid (ionicil quids) is by organic cation and inorganic or organic anion two portions are formed, the ionic system that under room temperature and adjacent temperature, is in a liquid state.Ionic liquid has the incomparable advantage of many other materials; Like the liquid temperature wide ranges, there is not significant vp, Heat stability is good; Have acidity or superpower acidity; And acidity can be carried out modulation as required, and many mineral compound and organic cpds etc. are had good solubility, and electrochemical window is wide etc.Based on these characteristics, ionic liquid has a wide range of applications at aspects such as extracting and separating, catalyzed reaction, electrochemistry, is expected to become 21 century the most promising green solvent and one of catalyzer.As the friendly type catalyzer of a kind of novel environmental; Ionic liquid can overcome the separation of homogeneous catalyst and reclaim difficulty, to shortcomings such as environment pollute; Having homogeneous catalyst high reaction activity and heterogeneous catalyst simultaneously concurrently is prone to and the isolating advantage of product; In reactions such as acid catalyzed alkylation, acylations, hydrogenation, esterification and polymerization, have broad application prospects, its development research gets more and more people's extensive concerning just day by day.
In fact after positively charged ion was confirmed, acidity was by anionic essence decision for acidic ion liquid.Acidic ion liquid is divided into " Lewis acidic ion liquid " and " Br ō nsted acidic ion liquid ".The advantage of acidic ion liquid is an ionic liquid as the friendly type acid catalyst of a kind of novel environmental, and it is little to have corrodibility; Reaction conditions relaxes; Acidity can be regulated; Can recycle.Overcome the problem of environmental pollution that traditional Lewis acid catalyst brings, and in acid catalyzed reaction, shown good activity and selectivity.
(3) summary of the invention
The new purposes that the purpose of this invention is to provide a kind of acidic ion liquid applies it to the synthetic field of hormone medicine.Utilize acidic ion liquid not only can be used for reaction medium but also can be used as catalyst property, through changing processing condition such as reaction times and temperature of reaction, the green synthesis method of aldolization in the research hormone medicine.
The technical scheme that the present invention adopts is following:
A kind of synthesizing budesonide; Described compound method comprises the steps: being added to suc as formula in the acidic ion liquid shown in (II) suc as formula 16 Alpha-hydroxy Prednisolone Acetates shown in (I) and butyraldehyde-n; Reacted 1~10 hour down at 10~100 ℃; Reaction finishes, and reaction solution can obtain suc as formula the budesonide shown in (III) through aftertreatment; Said 16 Alpha-hydroxy Prednisolone Acetates and the butyraldehyde-n amount of substance ratio that feeds intake is 1: 2~5, and the mass ratio of said 16 Alpha-hydroxy Prednisolone Acetates and described acidic ion liquid is 1: 1~10; In the described acidic ion liquid, R is alkyl or the substituted alkyl of C1~C10, and described substituting group is sulfonic group or carboxyl, and L is HSO
4 2-, COO
-, BF
4 -, BF
6 -, AlCl
4 -Or CF
3SO
3 -
Among the present invention, described post-treating method is: reaction finishes, and reaction solution is used dichloromethane extraction, gets organic layer, uses distilled water wash, and with the dry organic layer of siccative, the evaporated under reduced pressure solvent obtains suc as formula the budesonide product shown in (III).
Preferably, suc as formula the acidic ion liquid shown in (II), the substituted alkyl among the R is a sulfonic group among the present invention, and L is HSO
4 2-
Further, temperature of reaction of the present invention is preferably 50 ℃~80 ℃.
Further, the reaction times of the present invention is 3~5 hours.
Further, 16 Alpha-hydroxy Prednisolone Acetates according to the invention be preferably 1: 2 with the amount of substance ratio of butyraldehyde-n~3.
Further again, the mass ratio of said 16 Alpha-hydroxy Prednisolone Acetates and acidic ion liquid is preferably 1: 2~and 5.
Siccative described in the present invention is an anhydrous magnesium sulfate.
Comparatively concrete; Synthesizing budesonide according to the invention is carried out as follows: will be added to suc as formula in the acidic ion liquid shown in (II) suc as formula 16 Alpha-hydroxy Prednisolone Acetates shown in (I) and butyraldehyde-n; Reacted 3~5 hours down at 50~80 ℃; Reaction finishes, and reaction solution can obtain suc as formula the budesonide shown in (III) through aftertreatment; The amount of substance ratio of said 16 Alpha-hydroxy Prednisolone Acetates and butyraldehyde-n is 1: 2~3, and the mass ratio of said 16 Alpha-hydroxy Prednisolone Acetates and acidic ion liquid is 1: 2~5; In the acidic ion liquid shown in (II), R is a sulfonic group, and L is HSO
4 2-Described post-treating method is: reaction finishes, and reaction solution is used dichloromethane extraction, gets organic layer, distilled water wash, and the anhydrous magnesium sulfate drying organic layer, the evaporated under reduced pressure solvent obtains suc as formula the budesonide product shown in (III).
The present invention compared with prior art, its beneficial effect is embodied in: this technology is easy to operate, production capacity is high, excellent in efficiency, the three wastes are few, convenient post-treatment, ionic liquid is reusable, is economical and practical green environmental protection technique.
(4) embodiment
Below in conjunction with specific embodiment the present invention is described further, but protection scope of the present invention is not limited in this.
Embodiment 1
With 0.1g (2.66 * 10
-4Mol) 16 Alpha-hydroxy Prednisolone Acetates (I), 0.04g (5.32 * 10
-4Mol) the methylbutyl sulfonic group imidazoles vitriol acidic ion liquid of butyraldehyde-n and 0.2g adds in the reaction flask, maintains the temperature at 80 ℃, reacts 3 hours.Reaction process is used the TLC tracking monitor, and with hexanaphthene: the mixed solvent of acetone (volume ratio)=5: 5 disappears until raw material point as developping agent.Use 5 * 3mL dichloromethane extraction then, combining extraction liquid is behind 3 * 5mL distilled water wash; Tell organic layer; Behind the anhydrous magnesium sulfate drying, underpressure distillation gets white solid product budesonide (III) 0.11g to constant weight; Raw material 16-α hydroxyl Prednisolone Acetate (I) transformation efficiency is 100%, and yield is 95%.
Embodiment 2
With 0.1g (2.66 * 10
-4Mol) 16 Alpha-hydroxy Prednisolone Acetates (I), 0.06g (7.98 * 10
-4Mol) the methyl capric acid base imidazoles vitriol acidic ion liquid of butyraldehyde-n and 1g adds in the reaction flask, maintains the temperature at 50 ℃, reacts 10 hours.Reaction process is used the TLC tracking monitor, and with hexanaphthene: the mixed solvent of acetone (volume ratio)=5: 5 disappears until raw material point as developping agent.Use 5 * 3mL dichloromethane extraction then, combining extraction liquid is behind 3 * 5mL distilled water wash; Tell organic layer; Behind the anhydrous magnesium sulfate drying, underpressure distillation gets white solid product budesonide (III) 0.1g to constant weight; Raw material 16 Alpha-hydroxy Prednisolone Acetate (I) transformation efficiencys are 100%, and yield is 90%.
Embodiment 3
With 0.1g (2.66 * 10
-4Mol) 16 Alpha-hydroxy Prednisolone Acetates (I), 0.06g (7.98 * 10
-4Mol) the methylbutyl imidazoles trifluoro sulfinic acid salt acidic ion liquid of butyraldehyde-n and 1g adds in the reaction flask, maintains the temperature at 50 ℃, reacts 1 hour.Reaction process is used the TLC tracking monitor, and with hexanaphthene: the mixed solvent of acetone (volume ratio)=5: 5 disappears until raw material point as developping agent.Use 5 * 3mL dichloromethane extraction then, combining extraction liquid is behind 3 * 5mL distilled water wash; Tell organic layer; Behind the anhydrous magnesium sulfate drying, underpressure distillation gets white solid product budesonide (III) 0.11g to constant weight; Raw material 16 Alpha-hydroxy Prednisolone Acetate (I) transformation efficiencys are 100%, and yield is 95%.
Embodiment 4
With 0.1g (2.66 * 10
-4Mol) 16 Alpha-hydroxy Prednisolone Acetates (I), 0.04g (5.32 * 10
-4Mol) the acid ionic liquid of the methylbutyl sulfonic group imidazoles acetate of butyraldehyde-n and 0.2g adds in the reaction flask, maintains the temperature at 80 ℃, reacts 3 hours.Reaction process is used the TLC tracking monitor, and with hexanaphthene: the mixed solvent of acetone (volume ratio)=5: 5 disappears until raw material point as developping agent.Use 5 * 3mL dichloromethane extraction then, combining extraction liquid is behind 3 * 5mL distilled water wash; Tell organic layer; Behind the anhydrous magnesium sulfate drying, underpressure distillation gets white solid product budesonide (III) 0.1g to constant weight; Raw material 16 Alpha-hydroxy Prednisolone Acetate (I) transformation efficiencys are 100%, and yield is 89%.
Embodiment 5
With 0.1g (2.66 * 10
-4Mol) 16 Alpha-hydroxy Prednisolone Acetates (I), 0.04g (5.32 * 10
-4Mol) the methylbutyl imidazoles chloro-aluminate acidic ion liquid of butyraldehyde-n and 0.2g adds in the reaction flask, maintains the temperature at 100 ℃, reacts 10 hours.Reaction process is used the TLC tracking monitor, and with hexanaphthene: the mixed solvent of acetone (volume ratio)=5: 5 disappears until raw material point as developping agent.Use 5 * 3mL dichloromethane extraction then, combining extraction liquid is behind 3 * 5mL distilled water wash; Tell organic layer; Behind the anhydrous magnesium sulfate drying, underpressure distillation gets white solid product budesonide (III) 0.093g to constant weight; Raw material 16 Alpha-hydroxy Prednisolone Acetate (I) transformation efficiencys are 100%, and yield is 80%.
Embodiment 6
With 0.1g (2.66 * 10
-4Mol) 16 Alpha-hydroxy Prednisolone Acetates (I), 0.04g (5.32 * 10
-4Mol) the Methyl Octyl imidazoles hexafluorophosphate acidic ion liquid of butyraldehyde-n and 0.2g adds in the reaction flask, maintains the temperature at 100 ℃, reacts 1 hour.Reaction process is used the TLC tracking monitor, and with hexanaphthene: the mixed solvent of acetone (volume ratio)=5: 5 disappears until raw material point as developping agent.Use 5 * 3mL dichloromethane extraction then, combining extraction liquid is behind 3 * 5mL distilled water wash; Tell organic layer; Behind the anhydrous magnesium sulfate drying, underpressure distillation gets white solid product budesonide (III) 0.096g to constant weight; Raw material 16 Alpha-hydroxy Prednisolone Acetate (I) transformation efficiencys are 100%, and yield is 86%.
Claims (9)
1. synthesizing budesonide; It is characterized in that described compound method comprises the steps: being added to suc as formula in the acidic ion liquid shown in (II) suc as formula 16 Alpha-hydroxy Prednisolone Acetates shown in (I) and butyraldehyde-n; Reacted 1~10 hour down at 10~100 ℃; Reaction finishes, and reaction solution can obtain suc as formula the budesonide shown in (III) through aftertreatment; Said 16 Alpha-hydroxy Prednisolone Acetates and the butyraldehyde-n amount of substance ratio that feeds intake is 1: 2~5, and the mass ratio of said 16 Alpha-hydroxy Prednisolone Acetates and described acidic ion liquid is 1: 1~10; In the described acidic ion liquid, R is alkyl or the substituted alkyl of C1~C10, and described substituting group is a sulfonic group, and L is COO
-, BF
4 -, BF
6 -, AlCl
4 -Or CF
3SO
3 -
2. synthesizing budesonide as claimed in claim 1; It is characterized in that described post-treating method is: reaction finishes, and reaction solution is used dichloromethane extraction, gets organic layer; Use distilled water wash; With the dry organic layer of siccative, the evaporated under reduced pressure solvent obtains suc as formula the budesonide product shown in (III).
3. synthesizing budesonide as claimed in claim 1 is characterized in that suc as formula the acidic ion liquid shown in (II), the substituting group among the R is a sulfonic group.
4. synthesizing budesonide as claimed in claim 1 is characterized in that described temperature of reaction is 50 ℃~80 ℃.
5. synthesizing budesonide as claimed in claim 1 is characterized in that the described reaction times is 3~5 hours.
6. synthesizing budesonide as claimed in claim 1 is characterized in that the said 16 Alpha-hydroxy Prednisolone Acetates and the ratio of the amount of substance of butyraldehyde-n are 1: 2~3.
7. synthesizing budesonide as claimed in claim 1 is characterized in that the mass ratio of said 16 Alpha-hydroxy Prednisolone Acetates and acidic ion liquid is 1: 2~5.
8. synthesizing budesonide as claimed in claim 1; It is characterized in that said compound method carries out as follows: will be added to suc as formula in the acidic ion liquid shown in (II) suc as formula 16 Alpha-hydroxy Prednisolone Acetates shown in (I) and butyraldehyde-n; Reacted 3~5 hours down at 50~80 ℃; Reaction finishes, and reaction solution can obtain suc as formula the budesonide shown in (III) through aftertreatment; The amount of substance ratio of said 16 Alpha-hydroxy Prednisolone Acetates and butyraldehyde-n is 1: 2~3, and the mass ratio of said 16 Alpha-hydroxy Prednisolone Acetates and acidic ion liquid is 1: 2~5; In the acidic ion liquid shown in (II), R is alkyl or the substituted alkyl of C1~C10, and described substituting group is a sulfonic group, and L is COO
-, BF
4 -, BF
6 -, AlCl
4 -Or CF
3SO
3 -Described post-treating method is: reaction finishes, and reaction solution is used dichloromethane extraction, gets organic layer, distilled water wash, and the anhydrous magnesium sulfate drying organic layer, the evaporated under reduced pressure solvent obtains suc as formula the budesonide product shown in (III).
9. synthesizing budesonide as claimed in claim 2 is characterized in that said siccative is an anhydrous magnesium sulfate.
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CN101885751A (en) * | 2010-07-08 | 2010-11-17 | 仙居县力天化工有限公司 | Method for synthesizing desonide |
CN102060906B (en) * | 2010-12-23 | 2013-01-16 | 鲁南贝特制药有限公司 | Preparation method of R budesonide |
CN109485689B (en) * | 2019-01-08 | 2020-03-27 | 黑龙江中医药大学 | Preparation method of budesonide for treating infantile asthma |
Citations (2)
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WO2005044759A2 (en) * | 2003-08-14 | 2005-05-19 | Sun Pharmaceutical Industries Limited | Acetalization process for preparation of steroid compounds |
US20080281001A1 (en) * | 2006-10-25 | 2008-11-13 | Revalesio Corporation | Mixing device |
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WO2005044759A2 (en) * | 2003-08-14 | 2005-05-19 | Sun Pharmaceutical Industries Limited | Acetalization process for preparation of steroid compounds |
US20080281001A1 (en) * | 2006-10-25 | 2008-11-13 | Revalesio Corporation | Mixing device |
Non-Patent Citations (2)
Title |
---|
赵贞贞.2009101550582.《STN检索记录》.2011, * |
邵丽丽.咪唑类离子液体在有机反应中催化性能的研究.《硕士学位论文》.2008,第1章第14页. * |
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