CN101117350A - Method for preparing steroids and novel intermediate compound used therein - Google Patents
Method for preparing steroids and novel intermediate compound used therein Download PDFInfo
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- CN101117350A CN101117350A CNA200610015112XA CN200610015112A CN101117350A CN 101117350 A CN101117350 A CN 101117350A CN A200610015112X A CNA200610015112X A CN A200610015112XA CN 200610015112 A CN200610015112 A CN 200610015112A CN 101117350 A CN101117350 A CN 101117350A
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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Abstract
The present invention relates to an improved preparation method of glucocorticoids steroid, in particular to the preparation methods of prednisolone acetate, cortisone, prednisolone or hydrocortisone. The present invention also relates to a new intermediate compound used in the process of preparing the compounds. The present invention provides a new synthetic route of iodo first and opening the ring after, improving the selectivity of final products, reducing the impurity content of the products, and satisfying the color scale of glucocorticoids drugs, thereby conquering the disadvantages of preparing 17 alpha- hydroxyl at first, and then preparing 21-hydroxyl or the derivatives during the process of preparing 17 alpha, 21-hydroxyl steroid or the derivatives of prior art.
Description
Technical field
The present invention relates to a kind of improved preparation method of steroide of glucocorticoids, more particularly relate to the preparation method of Prednisone acetate, prednisolone, cortisone or hydrocortisone.The invention still further relates to new intermediate at the preparation above-claimed cpd.
Background technology
There are two main approach in the preparation of steroid class medicine now, and a kind of is the microbial transformation approach, and a kind of is the chemosynthesis approach.And for 17 α, the preparation of the dihydric steroide or derivatives thereof of 21-, traditional synthesis technique all is at first to prepare 17 Alpha-hydroxies, prepares 21-hydroxyl or derivatives thereof then.With 16, the 17-epoxide carries out ring-opening reaction as raw material and introduces 17 Alpha-hydroxies earlier, the approach of refabrication 21-hydroxyl is a synthesis technique relatively more commonly used, in being converted into the process of hydroxyl, 21 hydrogen comprise by microbial transformation (US2874172A), perhaps, be converted into the method (US2998436A) of hydroxyl or its acetic ester then by 21 iodo.But the mentioned microorganism method for transformation production cycle is long, and needs to use chloroform or methyl alcohol repeatedly to extract as extraction agent, causes the yield of the finished product to reduce; And the chemical synthesis process of first open loop, back iodo can influence the structure of the finished product, and for example 20-ketone may be converted into hydroxyl or 17,20 Cheng Huan, and the foreign matter content of the finished product increases.
Therefore, in order to overcome the above-mentioned defective of prior art, the invention provides a kind of improving one's methods of steroide that prepare, comprise the displacement of first iodo, the synthetic route of open loop again, improved the selectivity of final product, reduced foreign matter content, and made its look that meets the glucocorticosteroid similar drug ℃ standard.
Summary of the invention
An object of the present invention is to provide preparation formula is III and IV compound:
Wherein ... represent singly-bound or do not exist, X representative=O or OH (when ... representative is not when existing), H (when ... when representing singly-bound), R represents ethanoyl, and ring A and B represent following residue:
W represents the protecting group of O or following formula oxo base:
N is 2 or 3; R
2Represent ether or ester residue.
Another object of the present invention has provided III and IV compounds process for production thereof:
(a) be catalyzer and be in the presence of the organic solvent at inorganics, formula II compound and I with one or more of lower aliphatic alcohols, ketone, halohydrocarbon, ether solvent with calcium
2Reaction generates the formula III compound,
II III
Ring A and B ..., X defines suc as formula IV.
(b) in the presence of with one or more organic solvents of lower aliphatic alcohols, ketone, halohydrocarbon, ether solvent, formula III compound and MOR reaction production IV compound,
Wherein M represents basic metal; Ring A and B ..., X, R define suc as formula IV.
The organic solvent that uses in the step (a) is as the organic solvent of routine, as lower aliphatic alcohols, and particular methanol, ethanol; Ketone, preferred acetone; Halohydrocarbon, preferred chloroform; In the tetrahydrofuran (THF) etc. one or more.More preferably methyl alcohol, chloroform or tetrahydrofuran (THF), most preferably methyl alcohol, tetrahydrofuran (THF) or their mixture.The catalyzer that uses in the step (a) is the catalyzer of the carried iodine of routine, preferred calcium oxide (CaO).
Organic solvent in the step (b) is conventional organic solvent, comprises lower aliphatic alcohols, as methyl alcohol or ethanol; Ketone is as acetone; Halohydrocarbon is as chloroform; In the tetrahydrofuran (THF) etc. one or more.Preferred alcohol or acetone, more preferably acetone.Preferred sodium of the basic metal of MOR in this step or potassium, more preferably potassium, and preferred sodium-acetate of MOR or Potassium ethanoate, more preferably Potassium ethanoate.
In preferred version of the present invention, preferred preparation R is the formula IV compound of ethanoyl.
Be preferable over preparation X and be OH or=the formula IV compound of O.
In another preferred scheme of the present invention, preferred preparation ring A and B represent the formula IV compound of the residue of formula (1) or (2), and more preferably preparing wherein, W represents O; representative does not exist; X representative=O or OH, preferred representative=O, R represents the formula IV compound of H or ethanoyl.
In another optimized technical scheme of the present invention, preferred preparation ring A and B represent the formula IV compound of the residue of formula (1) or (2), and more preferably wherein W represents O ... represent singly-bound, X represents H, and R represents the formula IV compound of H or ethanoyl.
Work as R
2When representing the ether residue; it can be any residue that is used for protecting 3 of this structural formulas well known by persons skilled in the art, particularly contain 1-6 carbon atom alkyl, contain 3-8 carbon atom alkoxy alkoxy alkyl, contain the method for 6-10 carbon atom or contain the aralkyl of 7-12 carbon atom.
Work as R
2When representing alkyl, it can be methyl, ethyl, propyl group, sec.-propyl, normal-butyl, sec-butyl, the tertiary butyl, amyl group or hexyl.
Work as R
2During the representation alkoxy alkoxyalkyl, preferred methoxy ethoxy methyl.
Work as R
2When representing aralkyl, preferred benzyl or styroyl.
Work as R
2When representing aryl, the phenyl of preferred phenyl or replacement, for example phenyl that is replaced by one or more alkyl.
Work as R
2When representing the ester residue, it can be any residue that is used for protecting 3 of this structural formulas well known by persons skilled in the art, particularly-and COR
2, R
2As defined above.
Preparation III or IV compound are very useful as intermediates of synthetic gonane parahormone compound, the invention provides a kind of new improving one's methods for preparing gonane parahormone compound, formula III that it prepares or IV compound, can be used as intermediate preparation gonane parahormone compound, especially for the steroid compound of glucocorticoids, for example Prednisone acetate, prednisolone acetate, prednisolone, cortisone or hydrocortisone.This novel method is compared original old technology and is had greater advantage, has to improve yield, satisfy characteristics such as product colourity requirement.
Another object of the present invention provides the method for a kind of preparation formula (I) compound,
Wherein ... represent singly-bound or do not exist, X representative=O or OH (when ... representative is not when existing), H (when ... when representing singly-bound), R represents ethanoyl, R
1Represent H or ethanoyl, and ring A and B represent following residue:
W represents the protecting group of O or following formula oxo base:
N is 2 or 3; R
2Represent ether or ester residue.
Described method comprises:
(a) under acidic conditions, formula IV compound and hydrogen halide carry out ring-opening reaction production V compound,
Wherein encircle A and B ..., X, R define suc as formula I, Hal represents halogen;
(b) with one or more of lower aliphatic alcohols, ketone, halohydrocarbon, ethers be solvent, in the presence of acidic medium and catalyzer, formula V compound dehalogenation generates R for reaction
1Be the formula I compound of H,
(c) if necessary, R
1For the formula I compound of H further with MOR (M is a basic metal, and R is an ethanoyl), in the presence of organic solvent, prepared in reaction R
1Formula I compound for ethanoyl.
The acidic conditions of step (a) is to help the acidic medium that compound and hydrogen halide react, preferred acetate, diacetyl oxide or its mixture, more preferably acetate.
Organic solvent in the step (b) is conventional organic solvent, comprises lower aliphatic alcohols, as methyl alcohol or ethanol; Ketone is as acetone; Halohydrocarbon is as chloroform; In the tetrahydrofuran (THF) etc. one or more.Preferred alcohol and acetone, more preferably acetone.The preferred acetate of acidic medium, diacetyl oxide or its mixture, more preferably acetate.Catalyzer preferable alloy catalyzer, more preferably Raney's nickel catalyst.
Preferred sodium of basic metal or the potassium of MOR in the step (c), more preferably potassium, and preferred sodium-acetate of MOR or Potassium ethanoate, more preferably Potassium ethanoate.
Particularly, the present invention preferably provides a kind of preparation ring A and B representative (1) or (2) residue, and more preferably W represents the method for the formula I compound of O.
Be used to prepare the formula I compound that R is an ethanoyl in the scheme of the present invention.
Another scheme is to be used to prepare R
1Formula I compound for H.
Another scheme is that to be used to prepare R be ethanoyl and R
1Be H formula I compound.
Be preferred for preparation ... for singly-bound, X is the formula I compound of H.
Be preferred for preparation ... for do not exist, X is the formula I compound of=O.
In another optimized technical scheme, the present invention is used for the residue that preparation ring A and B represent formula (2), and wherein W represents O ... representative does not exist, and X representative=O, R represent H or ethanoyl, R
1Method for the formula I compound of H.
In another optimized technical scheme, invention is used for the residue that preparation ring A and B represent formula (2), and wherein W represents O ... representative does not exist, and X represents OH, and R represents H or ethanoyl, R
1Method for the formula I compound of H.
In preferred technical scheme, the present invention is used for the residue that preparation ring A and B represent formula (1), and wherein W represents O ... representative does not exist, X representative=O, and R represents ethanoyl, R
1Be the formula I compound of H, i.e. Prednisone acetate.
The synthetic route of preferred preparation Prednisone acetate is as follows:
Wherein the reaction conditions of Step1 is preferably methyl alcohol, tetrahydrofuran (THF), CaO/I
2
The reaction conditions of Step2 is preferably acetone and Potassium ethanoate.
The reaction conditions of Step3 is preferably acetic acid, HBr.
The reaction conditions of Step4 is preferably acetone, acetic acid, Raney's nickel.
Wherein the synthetic method of raw material Sml can be referring to preparing as disclosed synthetic route among the US2874172A.
In another preferred embodiment, the present invention is used for preparation ... represent singly-bound, X represents OH, and R is an ethanoyl, R
1Method for the formula I compound of H.
The reaction conditions of Step5 is preferably methyl alcohol, tetrahydrofuran (THF), CaO/I
2
The reaction conditions of Step6 is preferably acetone and Potassium ethanoate.
The reaction conditions of Step7 for the material that hypobromous acid can be provided at organic solvent, react in the preferred tetrahydrofuran (THF), preferably in tetrahydrofuran (THF), carry out the bromine hydroxylation reaction with NBS.
The reaction conditions of Step8 can be referring to Barton, and disclosed method is prepared among the et al (JACS, 1966,88,3016), for example makes solvent with DMS, chromium acetate catalysis, and butanethiol is made hydrogen transference reagent, total recovery 80%.Perhaps referring to Joel, et al (WO8901482A1, on February 23rd, 1989 is open) this method has been carried out process modification, make hydrogen donor with sulfydryl lipid acid (generally using Thiovanic acid), zinc powder/chromium chloride is made catalyzer, gentleness successfully removes 9-position halogen, and yield reaches more than 90%, and 9 (11) two key by products only are 1%-2%.
The reaction conditions of Step3 and Step4 is the same.
Wherein the synthetic method of raw material Sm6 can be referring to R.Rausser, A.M.Lyncheski, et al., (J.O.C.1966 (31), 26) report utilize CH
3SO
2Cl carries out the sulphur esterification to 11 α-OH steroidal compounds, utilizes NaOAc, HOAc to eliminate reaction again and forms Δ 9 (11) compounds.Perhaps Sm6 is synthetic can be that raw material uses method same as described above to obtain with the compound a.
Change and thing a can prepare referring to the synthetic method as US3037914.
By method of the present invention, the steroid compounds that obtains has following advantage:
(1) the last iodization yield that carries out again after than the open loop debrominate of the yield of going up iodine, open loop again improves greatly.
(2) the product content of the last iodization that carries out again after than the open loop debrominate of the content of going up iodization, open loop again improves a lot.
(3) the finished product such as Prednisone acetate crude product appearance color obviously bleach, and meet the color standard of medicine.
Although for the bright purpose of condition discloses preferred embodiment of the present invention, it will be appreciated by those skilled in the art that under situation about not breaking away from, can carry out various modifications, increase and replacement to the present invention by the spirit and scope of the present invention.
Embodiment
Embodiment 1
30ml methyl alcohol and 8 gram iodine are stirred to make iodine liquid standby.60ml tetrahydrofuran (THF), 6 gram calcium oxide, 10 gram Sml are dropped in the reaction flasks, stir after 10 minutes,, slowly drip iodine liquid, add back stirring 3 hours, be diluted among 10% acetic acid/water (V/V) 500ml, stir after 1 hour in 15-20 ℃, filter Sm2.mp:132~140℃。Its infrared data is as follows:
3000-2800,1728,1658,1630,1620,1475-1400,1372-1300,1155cm
-1.
Embodiment 2
60ml acetone, Sm2 are dropped in the reaction flask, stirs and add Potassium ethanoate 8 after 10 minutes and restrain and be warming up to 60-70 ℃, be incubated after 4 hours, reduce to 40 ℃ of concentrating under reduced pressure, be diluted in the 500ml water after having mass crystallization to occur, stir 1 hour after-filtration, be washed to neutrality, dry, get Sm3 solid 10.53 grams.mp:205~209℃。Its infrared data is as follows:
3000-2800,1746,1728,1658,1630,1620,1475-1400,1372-1300,1155cm
-1.
Embodiment 3
Hydrogen bromide/water (V/V) solution and the 30ml acetic acid of 30ml50-55% are added in the reaction flask, be cooled under 0 ℃ of stirring and slowly add the Sm310 gram, finish the back in 10 ℃ of insulations 3 hours, after reaction finishes, reaction solution is diluted in the 600ml water, is washed to neutrality and dries to such an extent that Sm4 is standby.
Embodiment 4
Sm4 is added in the reaction flask, add 60ml acetone, 20ml acetic acid is warming up to 50 ℃, feed nitrogen, add 10 gram Raney's nickels, under the vigorous stirring, slowly feed hydrogen, after 3 hours, reaction finishes, stop logical hydrogen, after the filtration, filtrate concentrating has only crystallization to separate out, be cooled to 0 ℃, be diluted in the 600ml water, filter, filter cake washes with water to neutrality, dries, and dries to such an extent that Sm5 solid 8.9 restrains.mp:233~238℃。Its infrared data is as follows:
3390,3000-2800,1747,1727,1659,1630,1620,1475-1400,1372-1300cm
-1.
Embodiment 5
30ml methyl alcohol and 7 gram iodine are stirred to make iodine liquid standby.50ml tetrahydrofuran (THF), 6.5 gram calcium oxide, 8 gram Sm6 are dropped in the reaction flasks, stir after 20 minutes,, slowly drip iodine liquid, add back stirring 6 hours, be diluted among 10% acetic acid/water (V/V) 500ml, stir after 1 hour in 15-30 ℃, filter Sm7.mp:126~132℃。Its infrared data is as follows: 3000-2800,1728,1658,1625,1620,1475-1400,1372-1300,1155cm
-1.
Embodiment 6
60ml acetone, Sm7 are dropped in the reaction flask, stirs and add Potassium ethanoate 9 after 10 minutes and restrain and be warming up to 70-80 ℃, be incubated after 4 hours, reduce to 40 ℃ of concentrating under reduced pressure, be diluted in the 500ml water after having mass crystallization to occur, stir 1 hour after-filtration, get Sm8 solid 10.1 grams.mp:194~198℃。Its infrared data is as follows: 3000-2800,1746,1728,1658,1625,1620,1475-1400,1372-1300,1155cm
-1.
Embodiment 7
90ml tetrahydrofuran (THF), 9 gram Sm8 are dropped in the reaction flask, be cooled to 15 ℃, stir after 10 minutes, the high chloro acid solution who adds the 0.48N of 48mL, the NBS that then adds 4.1 grams, stir after 4 hours, reduce to 25-30 ℃, in reaction mixture, add saturated metabisulfite solution to remove excessive hypobromous acid.Mixture filters with frozen water, collects filtrate, and washing is also dry, has to such an extent that Sm9 solid 10.8 restrains.mp:224~231℃。Its infrared data is as follows: 3000-2800,3392,1746,1728,1658,1620,1475-1400,1372-1300,1155cm
-1.
Embodiment 8
According to disclosed method among the W08901482A1, just adopt 10 gram Sm9 as raw material, at Thiovanic acid, under the condition of zinc powder/chromium chloride, remove 9-position halogen, get the Sm10 of 9.2 grams, its yield reaches 92%.mp:232~236℃。Its infrared data is as follows:
3000-2800,3392,1746,1728,1658,1620,1475-1400,1372-1300,1155cm
-1.
Embodiment 9
30ml methyl alcohol and 8 gram iodine are stirred to make iodine liquid standby.With 60ml tetrahydrofuran (THF), 6 gram calcium oxide, 11 grams 16,17-epoxy-pregnant steroid-4-alkene-3,11, the 20-triketone drops in the reaction flask, stirs after 10 minutes, in 15-20 ℃, slowly drip iodine liquid, add the back and stirred 4 hours, be diluted among 10% acetic acid/water (V/V) 500ml, stir after 1 hour, filter 16,17-epoxy-21-iodo-pregnant steroid-4-alkene-3,11, the 20-triketone.mp:127~134℃。Its infrared data is as follows: 3000-2800,1728,1645,1630,1625,1475-1400,1372-1300,1155cm
-1.
Embodiment 10
With 60ml ethanol, 9 grams 16,17-epoxy-21-iodo-pregnant steroid-4 alkene-3,11, the 20-triketone drops in the reaction flask, stirs to add Potassium ethanoate 10 after 10 minutes and restrain and be warming up to 50-70 ℃, is incubated after 4 hours, reduce to 40 ℃ of concentrating under reduced pressure, be diluted in the 500ml water after having mass crystallization to occur, stir 1 hour after-filtration, be washed to neutrality, dry, get 16,17-epoxy-21-hydroxyl-pregnant steroid-4-alkene-3,11,20-triketone-21 acetic ester solid 10.53 grams.mp:194.5~202℃。Its infrared data is as follows: 3000-2800,1746,1728,1645,1630,1624,1475-1400,1372-1300,1155cm
-1.
Embodiment 11
30ml methyl alcohol and 7 gram iodine are stirred to make iodine liquid standby.With 50ml tetrahydrofuran (THF), 6.5 gram calcium oxide, 10 grams 16,17-epoxy-pregnant steroid-4,9 (11)-diene-3,11, the 20-triketone drops in the reaction flask, stirs after 20 minutes, in 15-30 ℃, slowly drip iodine liquid, add the back and stirred 6 hours, be diluted among 10% acetic acid/water (V/V) 500ml, stir after 1 hour, filter 16,17-epoxy-21-iodo-pregnant steroid-4,9 (11)-diene-3, the 20-diketone.mp:121~128℃。Its infrared data is as follows: 3000-2800,1728,1646,1625,1626,1475-1400,1372-1300,1155cm
-1.
Embodiment 12
With 60ml ethanol, 16,17-epoxy-21-iodo-pregnant steroid-4,9 (11)-diene-3,11, the 20-triketone drops in the reaction flask, stirs to add sodium-acetate 9 after 10 minutes and restrain and be warming up to 70-80 ℃, be incubated after 4 hours, reduce to 40 ℃ of concentrating under reduced pressure, be diluted in the 500ml water after having mass crystallization to occur, stir 1 hour after-filtration, get 16,17-epoxy-21-hydroxyl-pregnant steroid-4,9 (11)-diene-3,20-diketone-21-acetic ester solid 10.1 grams.mp:186~191.5℃。Its infrared data is as follows: 3000-2800,1746,1728,1645,1625,1624,1475-1400,1372-1300,1155cm
-1.
Claims (10)
1. the method for a preparation formula (IV) compound,
Wherein ... represent singly-bound or do not exist, X representative=O or OH (when ... representative is not when existing), H (when ... when representing singly-bound), R represents ethanoyl, and ring A and B represent following residue:
W represents the protecting group of O or following formula oxo base:
N is 2 or 3; R
2Represent ether or ester residue, described method comprises:
(a) be catalyzer and be in the presence of the organic solvent at inorganics, formula II and I with one or more of lower aliphatic alcohols, ketone, halohydrocarbon, ether solvent with calcium
2Reaction generates formula III,
II III
Ring A and B ..., X defines suc as formula IV;
(b) in the presence of one or more organic solvent with lower aliphatic alcohols, ketone, halohydrocarbon, ether solvent, formula III and MOR reaction production IV,
Wherein M represents basic metal; Ring A and B ..., X, R define suc as formula IV.
2. the method for claim 1, wherein the organic solvent in the step (a) is selected from methyl alcohol, tetrahydrofuran (THF) and composition thereof, catalyzer is calcium oxide (CaO): the organic solvent of step (b) is selected from ethanol or acetone, and the acetate of M is selected from sodium-acetate or Potassium ethanoate.
6. the method for a preparation formula (I) compound,
Wherein ... represent singly-bound or do not exist, X representative=O or OH (when ... representative is not when existing), H (when ... when representing singly-bound), R represents ethanoyl, R
1Represent H or ethanoyl, and ring A and B represent following residue:
Or
W represents the protecting group of O or following formula oxo base:
N is 2 or 3; R
2Represent ether or ester residue.
Described method comprises:
(a) under acidic conditions, formula IV compound and hydrogen halide carry out ring-opening reaction production V compound,
Wherein encircle A and B ..., X, R define suc as formula I, Hal represents halogen;
(b) with one or more of lower aliphatic alcohols, ketone, halohydrocarbon, ethers be solvent, in the presence of acidic medium and catalyzer, formula V compound dehalogenation generates R for reaction
1Be the formula I compound of H,
(c) if necessary, R
1For the formula I compound of H further with MOR (M is a basic metal, and R is an ethanoyl), in the presence of organic solvent, prepared in reaction R
1Formula I compound for ethanoyl.
7. method as claimed in claim 6, in its described method:
Solvent is a lower fatty acid in the step (a), and hydrogen halide is a hydrogen bromide
The preferred ketone of solvent in the step (b); Acidic medium is lower fatty acid preferably; The preferred Raney's nickel of catalyzer.
Preferred Potassium ethanoate of MOR or sodium-acetate in the step (c); The preferred lower fatty acid of organic solvent.
8. as claim 6, wherein:
The preferred acetic acid of solvent in the step (a), hydrogen halide is preferably hydrogen bromide
The preferred acetone of solvent in the step (b); Acidic medium is acetic acid preferably; The preferred Raney's nickel of catalyzer.
Preferred Potassium ethanoate of MOR or sodium-acetate in the step (c); The preferred acetic acid of organic solvent.
9. the method for a preparation I compound, its Chinese style I compound is Sm5, it is characterized in that adopting following reaction scheme:
Wherein the reaction conditions of Step1 is methyl alcohol, tetrahydrofuran (THF), CaO/I
2The reaction conditions of Step2 is acetone and Potassium ethanoate; The reaction conditions of Step3 is acetic acid, HBr; The reaction conditions of Step4 is acetone, acetic acid and Raney's nickel.
10. the method for a preparation I compound, its Chinese style I compound is Sm12, it is characterized in that adopting following reaction scheme:
Wherein the reaction conditions of Step5 is methyl alcohol, tetrahydrofuran (THF), CaO/I
2The reaction conditions of Step6 is acetone and Potassium ethanoate; The reaction conditions of Step7 is tetrahydrofuran (THF) and NBS; The reaction conditions of Step8 is DMS, chromium acetate and butanethiol; Perhaps use sulfydryl lipid acid, and zinc powder/chromium chloride is made catalyzer; The reaction conditions of Step3 is acetic acid, HBr; The reaction conditions of Step4 is acetone, acetic acid and Raney's nickel.
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102617686A (en) * | 2012-03-16 | 2012-08-01 | 浙江凯迪药业有限公司 | Preparation method of prednisone |
CN102746357A (en) * | 2011-04-22 | 2012-10-24 | 天津金耀集团有限公司 | Technology for synthesizing reduced steroid |
CN103304615A (en) * | 2013-07-10 | 2013-09-18 | 赵云现 | Preparation method of cortisone |
-
2006
- 2006-08-03 CN CNA200610015112XA patent/CN101117350A/en active Pending
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102746357A (en) * | 2011-04-22 | 2012-10-24 | 天津金耀集团有限公司 | Technology for synthesizing reduced steroid |
CN102617686A (en) * | 2012-03-16 | 2012-08-01 | 浙江凯迪药业有限公司 | Preparation method of prednisone |
CN103304615A (en) * | 2013-07-10 | 2013-09-18 | 赵云现 | Preparation method of cortisone |
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