US2883403A - Process for conversion of 3beta,17alpha-dihydroxy-5-pregnene-11,20-dione to cortisone acetate - Google Patents
Process for conversion of 3beta,17alpha-dihydroxy-5-pregnene-11,20-dione to cortisone acetate Download PDFInfo
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- US2883403A US2883403A US719170A US71917058A US2883403A US 2883403 A US2883403 A US 2883403A US 719170 A US719170 A US 719170A US 71917058 A US71917058 A US 71917058A US 2883403 A US2883403 A US 2883403A
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- United States
- Prior art keywords
- pregnene
- dione
- hydroxy
- acetoxy
- dihydroxy
- Prior art date
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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 description 12
- 229960003290 cortisone acetate Drugs 0.000 title claims description 12
- 238000000034 method Methods 0.000 title claims description 6
- 238000006243 chemical reaction Methods 0.000 title description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- 230000001476 alcoholic effect Effects 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 235000011056 potassium acetate Nutrition 0.000 claims description 3
- 235000009518 sodium iodide Nutrition 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- NYZPTLBOPZZLRX-KJQYFISQSA-N (8S,9S,10R,13S,14S,17S)-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,3,4,7,8,9,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-11-one Chemical compound OCC([C@H]1CC[C@H]2[C@@H]3CC=C4CCCC[C@]4(C)[C@H]3C(C[C@]12C)=O)=O NYZPTLBOPZZLRX-KJQYFISQSA-N 0.000 claims 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims 1
- 229910052804 chromium Inorganic materials 0.000 claims 1
- 239000011651 chromium Substances 0.000 claims 1
- 238000011084 recovery Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 6
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 6
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 6
- 229960004544 cortisone Drugs 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- -1 acetoxyl group Chemical group 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000008707 rearrangement Effects 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- UOQFZGVGGMHGEE-UHFFFAOYSA-N 1,1-dihydroxypropan-2-one Chemical group CC(=O)C(O)O UOQFZGVGGMHGEE-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- KPVWDKBJLIDKEP-UHFFFAOYSA-L dihydroxy(dioxo)chromium;sulfuric acid Chemical compound OS(O)(=O)=O.O[Cr](O)(=O)=O KPVWDKBJLIDKEP-UHFFFAOYSA-L 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- VZRAKVPDZIQRGT-WZBAXQLOSA-N (8r,9s,10s,13r,14s,17r)-17-ethenyl-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthrene Chemical compound C1CCC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C=C)[C@@H]4[C@@H]3CCC21 VZRAKVPDZIQRGT-WZBAXQLOSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- WKAVAGKRWFGIEA-UHFFFAOYSA-N 11-Ketoprogesterone Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(C(=O)C)C1(C)CC2=O WKAVAGKRWFGIEA-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000272194 Ciconiiformes Species 0.000 description 1
- 238000006036 Oppenauer oxidation reaction Methods 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 229940117975 chromium trioxide Drugs 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000004992 fission Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 238000006049 ring expansion reaction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Definitions
- This invention relates to a process for converting 35, 17a-dihydroxy-5-pregnene-l1,20-dione to cortisone acetate or cortisone.
- An object of the present invention is to provide a process for proceeding from 3B,17a-dihydroxy-5-pregnene- 11,20-dione to cortisone acetate which eliminates the Oppenauer oxidation and, more especially, the protective acetylation of the 17a-hydroxyl group.
- the latter reaction and the subsequent de-acetylation to l7a-hydroxyl cause an appreciable yield lowering at the final stages of cortisone manufacture where high yields are most significant.
- the C-21 function is an acetoxyl group, so it is not necessary to reacetylate the C-21 hydroxyl to obtain cortisone as its acetate, the usual product of commerce.
- the source material, 3/3,17a-dihydroxy-5-pregnene-1l, 20-dione, for the present process was prepared from 11- ketodiosgenin, as described in our copending application, Serial Number 644,184, filed March 5, 1957.
- Example 2 Preparation of 2I-acetoxy-17u-hydroxy-5-pregnene-3, 11,20-trione.
- a sample of the preceding preparation 1.35 g., was dissolved in 250 ml. of acetone (redistilled from potassium permanganate), cooled to 12 C. and treated with 1 ml. of an aqueous solution of 0.2672 g. chromium trioxide and 0.23 cc. of sulfuric acid. The reaction proceeded rapidly and within a minute a gray precipitate formed. After an additional two minutes passed, the reaction was stopped by dilution with 600 ml. of saline solution.
- the green solution gradually deposited a residue of pure white, flattened needles which were filtered off, washed with saline solution and with water.
- a sample was recrystallized from aqueous acetone to give pure 21- acetoxy-17a-hydroxy-5-pregnene 3,11,20 trione.
- the melting point depended somewhat on the rate of heating. Rapid determination on a preheated Kofler stage gave a value of ISO-183 C. A slower determination gave melting at 175 to a viscid mass that resolidified incompletely to short quadrangular forms reddening (decomposition) at 200 with final crystal disappearance at 220.
- Example 3 Preparation of cortisone acetate-A sample of 350 mg. of 21-acetoxy-l7a-hydroxy-5-pregnene-3,11,20-trione was dissolved in 50 ml. of methanol and 0.4 ml. of concentrated ammonia water (28%) was added. The mixture was let stand minutes and the steroid was precipitated by addition of saline. The product after crystallization from aqueous methanol was cortisone acetate identical in every respect with authentic cortisone acetate.
- Example 4 The isomerization was carried out identically with ample 3 except that the catalyst used was 0.4 ml. of 6 N HCl. The product was cortisone acetate.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
Description
S t Patent 2,883,403 BQGE FOR CONV SI N OF a v m DROXY-S-PREGNENE-11,20-DIONE T0 COR- TISONE ACETATE Edward S. Rothman, Philadelphia, and ,Monroe E. Wall, Oreland, Pa., assignbrs to the United States of America as represented by the secretarysofsAgricultnre Noni-swing. n pncarionlnareh 4, 1958 Serial-No. 719,170
'2 Claims. (or. 260--397.45)
(Granted under Title 35, US. 'Code (1952), see. 266) A non-exclusive, irrevocable, royalty-free license in the invention herein described, throughout the world for all purposes of the United States Government, with the power to grant sublicenses for such purposes, is hereby granted to the Government of the United States of America.
This invention relates to a process for converting 35, 17a-dihydroxy-5-pregnene-l1,20-dione to cortisone acetate or cortisone.
An object of the present invention is to provide a process for proceeding from 3B,17a-dihydroxy-5-pregnene- 11,20-dione to cortisone acetate which eliminates the Oppenauer oxidation and, more especially, the protective acetylation of the 17a-hydroxyl group. The latter reaction and the subsequent de-acetylation to l7a-hydroxyl cause an appreciable yield lowering at the final stages of cortisone manufacture where high yields are most significant. Furthermore, during all the final reactions of the process of this invention the C-21 function is an acetoxyl group, so it is not necessary to reacetylate the C-21 hydroxyl to obtain cortisone as its acetate, the usual product of commerce.
We have found that the desired A -3 keto moiety of cortisone can be obtained by oxidizing 2l-acetoxy-3fi,17adihydroxy-S-pregnene-l1,20-dione with chromic acid-sulfuric acid mixture in acetone medium. Not only is the dihydroxy acetone side chain stable under these conditions, but surprisingly, the undesirable rearrangements which often occur under acidic conditions did not take place. For example, undesired reactions such as fission of the entire easily-oxidizable dihydroxyacetone side chain, glycolic rearrangement of the l7a-hydroxyl group to the C-2l position to form a C-21 aldehyde group (known to occur when cortisone in methanolic hydrochloric acid is allowed to stand at room temperature) and D-homo rearrangement (D-ring expansion) did not occur.
The source material, 3/3,17a-dihydroxy-5-pregnene-1l, 20-dione, for the present process was prepared from 11- ketodiosgenin, as described in our copending application, Serial Number 644,184, filed March 5, 1957.
According to the present invention we brominate 3p, 17a-dihydroxy-5-pregnene-11,20-dione with two molecules of bromine thus to obtain 5,6,2l-tribromo-3 3,l7a-dihydroxyallopregnane-l1,20-dione. We then sequentially treat the product in acetone solution with sodium iodide and sodium or potassium acetate to obtain the new compound, 2l-acetoxy-3,B,17a-dihydroxy-5 pregnene ll,20- dione. Brief oxidation of this compound in acetone with chromic acid-sulfuric acid mixture gives a high yield of a new compound, isomeric with cortisone acetate, and differing from cortisone acetate only in the location of the double bond, viz. A instead of A. This new compound, 2l-acetoxy-l7a-hydroxy-5-pregnene-3,11,20-trione, is easily isomerized to 2'1-acetoxy-17a-hydroxy-4-pregnene-3,11,20-trione (cortisone acetate) by quite small (catalytic) amounts of acid or base, e.g. ammonia. The
-' improvements disclosed this invention l he 'clear' by the followingexamples.
'Example .l "Pre arazi n of .zzawerwt .aaira-ath ar' dwh I,
s .theCoursefif'l-QS hours; se-imelear bromineimdllifi'ii'tl. of carboii traehlo'ride wa'staddeii. this point "the entirequantity .6r. .sremia;as ,gpa'sied into sem'tion. Although attack at'C 2l seems to "go prererentially over addition at 5,6 we prefer to add a'second mole of bromine. It was sometimes necessary to add a little more chloroform in reactions where re-precipitation occurred or where turbidity developed. The second mole of bromine is taken up with some reluctance. At the end of the bromination solvents were removed in vacuo. The residue was dissolved in a liter of acetone and treated with 20 g. of sodium iodided with stirring at room temperature overnight. The steroids were isolated with ether and freed of iodine by very cautious treatment with a minimum of sodium thiosulfate solution. The solvents were again removed in vacuo and the steroids again dissolved in a liter of acetone containing 4 ml. of acetic acid and 20 g. of dry potassium acetate. The mixture was stirred at reflux for 12 hours and again steroidal matter w'asisolated with ether. The product was recrystallized from aqueous acetone to give needles dc-solvating at 97, and showing a double M.P. 112, 208-213", lai +33.0.
Example 2 Preparation of 2I-acetoxy-17u-hydroxy-5-pregnene-3, 11,20-trione.A sample of the preceding preparation, 1.35 g., was dissolved in 250 ml. of acetone (redistilled from potassium permanganate), cooled to 12 C. and treated with 1 ml. of an aqueous solution of 0.2672 g. chromium trioxide and 0.23 cc. of sulfuric acid. The reaction proceeded rapidly and within a minute a gray precipitate formed. After an additional two minutes passed, the reaction was stopped by dilution with 600 ml. of saline solution. The green solution gradually deposited a residue of pure white, flattened needles which were filtered off, washed with saline solution and with water. A sample was recrystallized from aqueous acetone to give pure 21- acetoxy-17a-hydroxy-5-pregnene 3,11,20 trione. The melting point depended somewhat on the rate of heating. Rapid determination on a preheated Kofler stage gave a value of ISO-183 C. A slower determination gave melting at 175 to a viscid mass that resolidified incompletely to short quadrangular forms reddening (decomposition) at 200 with final crystal disappearance at 220. The sample was nearly transparent to ultraviolet 239 mp radiation. E.=300 (methanol) without maximum. [a] =+44.3 (dioxane).
Example 3 Preparation of cortisone acetate-A sample of 350 mg. of 21-acetoxy-l7a-hydroxy-5-pregnene-3,11,20-trione was dissolved in 50 ml. of methanol and 0.4 ml. of concentrated ammonia water (28%) was added. The mixture was let stand minutes and the steroid was precipitated by addition of saline. The product after crystallization from aqueous methanol was cortisone acetate identical in every respect with authentic cortisone acetate.
Example 4 The isomerization was carried out identically with ample 3 except that the catalyst used was 0.4 ml. of 6 N HCl. The product was cortisone acetate.
"1'."A"piocess"for'converting 3,8,17a dihydroxy 5-pregnene-11,20-dione to cortisone acetate comprising brominetting ,318,1T/pudihydroxymregnene-1.1,-20- dione to obtain "SIGQZHribtnib-Sp,17a-clihydroxyallopregnane-11,20 dione, reacting the latter successively with sodium iodide and a reagent consisting ofacetic acid and a salt sestand in a medium selected from the group consisting of a basic alcoholic solution and an acidic alcoholic solution to isomerize 2l-acetoxy-17u-hydroxy-5-pregnene-3,11,20- trione to 21-acctoxy-17a-hydroxy 4 pregnene 3,11,20- trione. v
2.; 2l-acetoxy-17a-hydroxy-5-pregnene-3,1 1,20-trione.
References Cited in the file of this patent v UNITED STATES PATENTS 2,668,816- Miescher etal. Feb. 9, 1954 2,786,856 Cutler et a1 Mar. 26, 1957 2,787,623' Gebert Apr. 2, 1957 2,805,230 Stork et a1 Sept. 3, 1957
Claims (1)
1. A PROCESS FOR CONVERTING 3B,17A DIHYDROXY-5-PREG-ENE NENE-11,20-DIONE TO CORTISONE ACETATE COMPRISING BROMINATING 3B,17A-DIHYDROXY-5-PREGNENE-11,20-DIONE TO OBTAIN 5,6,21-TRIBROMO-3B,17A-DIHYDROXYALLOPREGNANE-11,20 - DIONE, REACTING THE LATTER SUCCESSIVELY WITH SODIUM IODIDE AND A REAGENT CONSISTING OF ACETIC ACID AND A SALT SELECTED FROM THE GROUP CONSISTING OF POTASSIUM ACETATE AND SODIUM ACETATE, AND RECOVERING 21-ACETOXY-3B,17A-DIYDROXY HYDROXY-5-PREGNENE-11,20-DIONE, ADDING CHROMIUM TRIOXIDE-SULFRIC ACID MIXTURE TO A COLD ACETONE SOLUTION OF THE 21-ACETOXY-3B,17A-DIHYDROXY-5-PREGNENE-11,20-DIONE TO OXIDIZE THE 3B-HYDROXY FUNCTION, RECOVERY 21-ACETOXY17A-HYDROXY-5-PREGNENE-3,11,20-TRIONE AND ALLOWING IT TO STAND IN A MEDIUM SELECTED FROM THE GROUP CONSISTING OF A BASIC ALCOHOLIC SOLUTION AND AN ACIDIC ALCOHOLIC SOLUTION TO ISOMERIZE 21-ACETOXY-17A-HYDROXY-5-PREGNENE-3,11,20TRIONE TO 21-ACETOXY-17A-HYDROXY-5-PREGNENE,3,11,20TRIONE. 2. 21-ACETOXY-17A-HYDROXY-5-PREGNENE-3,11,20-TRIONE.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US719170A US2883403A (en) | 1958-03-04 | 1958-03-04 | Process for conversion of 3beta,17alpha-dihydroxy-5-pregnene-11,20-dione to cortisone acetate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US719170A US2883403A (en) | 1958-03-04 | 1958-03-04 | Process for conversion of 3beta,17alpha-dihydroxy-5-pregnene-11,20-dione to cortisone acetate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2883403A true US2883403A (en) | 1959-04-21 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US719170A Expired - Lifetime US2883403A (en) | 1958-03-04 | 1958-03-04 | Process for conversion of 3beta,17alpha-dihydroxy-5-pregnene-11,20-dione to cortisone acetate |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2883403A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2998436A (en) * | 1957-03-05 | 1961-08-29 | Edward S Rothman | Intermediates in the conversion of 11-ketodiosgenin to cortisone |
| US3027368A (en) * | 1958-08-13 | 1962-03-27 | Syntex Sa | Process for the production of 6alpha-fluorocortisone-21-acetate and intermediates therein |
| US3084157A (en) * | 1957-10-15 | 1963-04-02 | Syntex Corp | Process for the production of 6alpha-fluorocortisone and intermediates therein |
| DE1159434B (en) * | 1960-03-21 | 1963-12-19 | Roussel Uclaf | Process for the production of 4-fluoro-3-keto-í¸-steroids of the pregnan, androstan and 19-nor-androstan series |
| DE1240856B (en) * | 1961-01-30 | 1967-05-24 | Roussel Uclaf | Process for the preparation of 4-fluoro-3-oxo-delta 4-steroids |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2668816A (en) * | 1950-02-10 | 1954-02-09 | Ciba Pharm Prod Inc | Process for the preparation of 17, 20-hydroxyketones of the pregnane series and new and useful compounds of the said series |
| US2786856A (en) * | 1954-03-22 | 1957-03-26 | Merck & Co Inc | Preparation of 21-acyloxy-3, 17alpha-dihydroxy-5, 6-dichloro-20-ketopregnane |
| US2787623A (en) * | 1954-09-30 | 1957-04-02 | William H Gebert | Reduction of 16-iodopregnane compounds |
| US2805230A (en) * | 1952-08-02 | 1957-09-03 | Syntex Sa | Esters of 17alpha-hydroxy progesterone |
-
1958
- 1958-03-04 US US719170A patent/US2883403A/en not_active Expired - Lifetime
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2668816A (en) * | 1950-02-10 | 1954-02-09 | Ciba Pharm Prod Inc | Process for the preparation of 17, 20-hydroxyketones of the pregnane series and new and useful compounds of the said series |
| US2805230A (en) * | 1952-08-02 | 1957-09-03 | Syntex Sa | Esters of 17alpha-hydroxy progesterone |
| US2786856A (en) * | 1954-03-22 | 1957-03-26 | Merck & Co Inc | Preparation of 21-acyloxy-3, 17alpha-dihydroxy-5, 6-dichloro-20-ketopregnane |
| US2787623A (en) * | 1954-09-30 | 1957-04-02 | William H Gebert | Reduction of 16-iodopregnane compounds |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2998436A (en) * | 1957-03-05 | 1961-08-29 | Edward S Rothman | Intermediates in the conversion of 11-ketodiosgenin to cortisone |
| US3084157A (en) * | 1957-10-15 | 1963-04-02 | Syntex Corp | Process for the production of 6alpha-fluorocortisone and intermediates therein |
| US3027368A (en) * | 1958-08-13 | 1962-03-27 | Syntex Sa | Process for the production of 6alpha-fluorocortisone-21-acetate and intermediates therein |
| DE1159434B (en) * | 1960-03-21 | 1963-12-19 | Roussel Uclaf | Process for the production of 4-fluoro-3-keto-í¸-steroids of the pregnan, androstan and 19-nor-androstan series |
| DE1240856B (en) * | 1961-01-30 | 1967-05-24 | Roussel Uclaf | Process for the preparation of 4-fluoro-3-oxo-delta 4-steroids |
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