DE1048274B - Process for the preparation of 11,17ª ‡ -Dioxy-21-fluoro-4-pregnen-3,20-diones substituted in the 6-position by a hydrocarbon radical - Google Patents
Process for the preparation of 11,17ª ‡ -Dioxy-21-fluoro-4-pregnen-3,20-diones substituted in the 6-position by a hydrocarbon radicalInfo
- Publication number
- DE1048274B DE1048274B DEU4718A DEU0004718A DE1048274B DE 1048274 B DE1048274 B DE 1048274B DE U4718 A DEU4718 A DE U4718A DE U0004718 A DEU0004718 A DE U0004718A DE 1048274 B DE1048274 B DE 1048274B
- Authority
- DE
- Germany
- Prior art keywords
- dioxy
- pregnen
- fluoro
- hydrocarbon radical
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 10
- 238000002360 preparation method Methods 0.000 title claims description 9
- 239000004215 Carbon black (E152) Substances 0.000 title claims description 7
- 229930195733 hydrocarbon Natural products 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 7
- 229910001512 metal fluoride Inorganic materials 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 229940096017 silver fluoride Drugs 0.000 description 7
- REYHXKZHIMGNSE-UHFFFAOYSA-M silver monofluoride Chemical compound [F-].[Ag+] REYHXKZHIMGNSE-UHFFFAOYSA-M 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 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 description 6
- -1 steroid compounds Chemical class 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- 229960000890 hydrocortisone Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- NWJJZHDRVSKTBB-YFWFAHHUSA-N 21-Fluoroprogesterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(=O)CF)[C@@H]4[C@@H]3CCC2=C1 NWJJZHDRVSKTBB-YFWFAHHUSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- 230000001919 adrenal effect Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 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 1
- 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 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000002296 eclampsia Diseases 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- VBTQNRFWXBXZQR-UHFFFAOYSA-N n-bromoacetamide Chemical compound CC(=O)NBr VBTQNRFWXBXZQR-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 201000011461 pre-eclampsia Diseases 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 210000002700 urine Anatomy 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Description
Verfahren zur Herstellung von in 6-Stellung durch einen Kohlenwasserstoffrest substituierten 11,17a-Dioxy-21-fluor-4-pregnen-3,20-dionen Gegenstand der Erfindung ist ein Verfahren zur Herstellung von in 6-Stellung durch einen Kohlenwasserstoffrest substituierten Steroidverbindungen, insbesondere von 6-Methyl-11fl,17a-dioxy-21-fluor-4-pregnen-3,20-dion.Process for the production of in 6-position by a hydrocarbon radical Substituted 11,17a-dioxy-21-fluoro-4-pregnen-3,20-diones are the subject of the invention is a process for the production of in 6-position by a hydrocarbon radical substituted steroid compounds, in particular of 6-methyl-11fl, 17a-dioxy-21-fluoro-4-pregnen-3,20-dione.
Das erfindungsgemäße Verfahren wird durch die folgende Gleichung erläutert: in der X einen Kohlenwasserstoffrest, wie den imethyl-, Äthyl-, Phenyl-, Tolyl- oder Naphthylrest, vorzugsweise aber den Methylrest, bedeutet.The method according to the invention is explained by the following equation: in which X is a hydrocarbon radical, such as the imethyl, ethyl, phenyl, tolyl or naphthyl radical, but preferably the methyl radical.
Das nach dem erfindungsgemäßen Verfahren herstellbare 6a-Methyl-llß,17a-dioxy-21-fluor-4-pregnen-3,20-dion ist physiologisch stark wirksam und besitzt ein Wirkungsspektrum, das von dem natürlich vorkommender Nebennierenrindenhormone, wie dem des Hydrocortisons und Cortisons, insbesondere hinsichtlich der Wirkung auf den Mineralien- und Wasser-Stoffwechsel verschieden ist. Das gleiche gilt für das 1 1-keto Derivat des 6a-Methyl-1 lß,17a-dioxy#21-fluor-4-pregnen-3,20-dions.The 6a-methyl-11ß, 17a-dioxy-21-fluoro-4-pregnen-3,20-dione which can be prepared by the process according to the invention is physiologically highly effective and has a spectrum of activity that is similar to that of naturally occurring adrenal hormones such as hydrocortisone and Cortisone, especially with regard to the effect on the mineral and water metabolism, is different. The same is true for the 1 1-keto derivative of 6a-methyl-1 LSS, 17a-dioxy # 21-fluoro-4-pregnene-3,20-dione.
Die neuen Verbindungen gemäß der Erfindung bewirken die Ausscheidung von Salz und Wasser, was sie für die Behandlung von chronischen kongestiven Herzbeschwerden und Leberzirrhosen sowie die Behandlung von nephrotischem Sydrom, Eclampsien und Präeclampsien besonders wertvoll macht. Sie besitzen ferner entzündungsmildernde, glucocorticoide, anäesthetische, uterine, ovariale, adrenalwachstumshemmende und adrenalcorticoide Wirksamkeit. Dabei ist z. B. die mit dem Granulomtest nach Andr6 Robert und Mitarbeiter (Acta Endocrinologica, Bd. 25, 1957, S. 105) ermittelte entzündungsmildernde Wirkung des6a-Methyl-Ilp,17a-dioxy-21-fluor-4-pregnen-3,20-dions 5,7mal so groß wie die des Hydrocortisons, während die entsprechende, in 6-Stellung nicht substituierte Verbindung keine entzündungsmildernde Wirkung aufweist. Der Leberglykogenablagerungstest ergab für das 6a-Methyl-llß,17a-dioxy-21-fluor-4-pregnen-3,20-dion den 2,4-fachen, [für die in 6-Stellung nicht substituierte Verbindung nur den 0,29 fachen Wert des Hydrocortisons. Ferner wird mit 6a-Methyl-llp,17a-dioxy-21-fluor-4-pregnen-3,20-dion eine um 250/,) erhöhte Salz- und eine um 60"/, erhöhte Urinausscheidung erreicht. Die in 6-Stellung keinen Kohlenwasserstoffrest enthaltende Verbindung weist eine derartige Wirkung nicht auf. Die 6ß-Epimeren der Erfindung haben die gleiche Wirkung wie die oben beschriebenen 6a-Epimeren.The new compounds according to the invention cause the excretion of salt and water, which makes them particularly valuable for the treatment of chronic congestive heart problems and liver cirrhosis and the treatment of nephrotic syndrome, eclampsia and preeclampsia. They also have anti-inflammatory, glucocorticoid, anesthetic, uterine, ovarian, adrenal growth-inhibiting and adrenalcorticoid activity. It is z. B. the anti-inflammatory effect of des6a-methyl-Ilp, 17a-dioxy-21-fluoro-4-pregnen-3,20- determined with the granuloma test according to Andr6 Robert and coworkers (Acta Endocrinologica, Vol. 25, 1957, p. 105) dione is 5.7 times larger than that of hydrocortisone, while the corresponding compound, which is not substituted in the 6-position, has no anti-inflammatory effect. The liver glycogen deposition test gave the 6a-methyl-11ß, 17a-dioxy-21-fluoro-4-pregnen-3,20-dione the 2.4-fold, [for the compound unsubstituted in the 6-position only the 0.29 times the value of hydrocortisone. Furthermore, with 6a-methyl-llp, 17a-dioxy-21-fluoro-4-pregnen-3,20-dione an increased salt excretion by 250% and an increased urine excretion by 60 "is achieved. The compound not containing a hydrocarbon residue does not have such an effect, and the 6β-epimers of the invention have the same effect as the 6α-epimers described above.
Das 6-Methyl-llß,17a-dioxy-21-fluor-4-pregnen-3,20-dion kann in Form oraler und parenteraler Präparate sowie in Form von Oberflächenpräparaten angewendet werden. Für die Herstellung zu verabreichender Präparate kann Polyäthylenglycol 4000 oder 6000 als Träger oder Lactose und/oder Sucrose als Verdünnungsmittel verwendet werden. Für die Oberflächenanwendung wird das 6a-Methyl-llß,17a-dioxy-21-fluor-4-pregnen-3,20-dion zu Salben, flüssigen Präparaten, Gelees, Cremes, Suppositorien, Zäpfchen, wäßrigen Suspensionen usw. verarbeitet. In gleicher Weise lassen sich natürlich auch in 6-Stellung durch andere Kohlenwasserstofireste substituierte 1 lp,17a-Dioxy-21-fluor-4-pregnen-3,20-dione für derartige Präparate verwenden.The 6-methyl-11ß, 17a-dioxy-21-fluoro-4-pregnen-3,20-dione can be used in the form of oral and parenteral preparations as well as in the form of surface preparations. For the preparation of preparations to be administered, polyethylene glycol 4000 or 6000 can be used as a carrier or lactose and / or sucrose as a diluent. For surface application, the 6a-methyl-11ß, 17a-dioxy-21-fluoro-4-pregnen-3,20-dione is processed into ointments, liquid preparations, jellies, creams, suppositories, suppositories, aqueous suspensions, etc. In the same way, 1 lp, 17a-dioxy-21-fluoro-4-pregnen-3,20-diones substituted in the 6-position by other hydrocarbon radicals can of course also be used for such preparations.
Die nach dem erfindungsgemäßen Verfahren herstellbaren Verbindungen, wie das 6-Mechyl-llß,17a-dioxy-21-fluor-4-pregnen-3,20-dion, sind auch als Ausgangsstoffe für die Herstellung weiterer physiologisch wichtiger Verbindungen, -wie der 9a-Halogeiianalogen, insbesondere des 6a-Methyl-9a,21-difluor-llß,17a-dioxy-4-pregnen-3,11,20-trions, nützlich. Bei der Durchführung des erfindungsgernäßen Verfahrens wird z. B. 6-Methyl-llß, 17a-dioxy-21-jod-4-pre,-nen-3,20-dion in einem geeigneten Lösungsmittel, z. B. Acetonitril, Hexan, Heptan, Benzol, tert.-Butylalkohol od. dgl., vorteilhaft in Acetonitril, in bekannter Weise mit Silberfluorid umgesetzt. Die Reaktion erfolgt unter Ausschluß von Licht und unter Rühren. Z-weckmäßig verwendet man eine 50 0/,ige wäßrige Silber-:fluoridlösung an Stelle von festem Silberfluorid. Die Reaktion wird bei einer Temperatur zwischen 40 und 60'C durchgeführt. Höhere oder niedrigere Temperaturen zwischen 10 und etwa 75'C sind ebenfalls anwendbar. Da das bei der Umsetzung entstehende Süberjodid mit dem Süberfluorid eine Molekülverbindung eingeht, müssen für eine theoretische Umsetzung mindestens 2 Mol Silber-:fluorid pro Mol Steroid vorhanden sein. Vorzugsweise verwendet man jedoch einen Überschuß von 10 bis 5001, und mehr über diese Menge, um höhere Ausbeuten zu erzielen. Das Silberfluorid wird nach und nach innerhalb eines bestimmten Zeitraums zugegeben. Die Reaktionszeit beträgt eine halbe Stunde bis sechs Stunden. Zur Isolierung des Produktes wird das Lösungsmittel verdampft und das Rohprodukt mit einem geeigneten Lösungsmittel, wie Chloroform, Methylenchlorid, Tetrachlorkohlenstoff, Benzol od. dgl., extrahiert. Die Reinigung erfolgt nach Üblichen Verfahren, z. B. durch weitere Extraktion zur Beseitigung von Verunreinigungen, Umkristallisieren oder nach Bedarf chromatographisch.The compounds which can be prepared by the process according to the invention, such as 6-Mechyl-11ß, 17a-dioxy-21-fluoro-4-pregnen-3,20-dione, are also used as starting materials for the preparation of other physiologically important compounds, such as 9a Halogen analogs, especially 6a-methyl-9a, 21-difluoro-11ß, 17a-dioxy-4-pregnen-3,11,20-trione, are useful. When carrying out the process according to the invention, for. B. 6-methyl-11ß, 17a-dioxy-21-iodo-4-pre, -nen-3,20-dione in a suitable solvent, e.g. B. acetonitrile, hexane, heptane, benzene, tert-butyl alcohol or the like, advantageously in acetonitrile, reacted in a known manner with silver fluoride. The reaction takes place with exclusion of light and with stirring. As a rule, a 50 % aqueous silver fluoride solution is used instead of solid silver fluoride. The reaction is carried out at a temperature between 40 and 60.degree. Higher or lower temperatures between 10 and about 75 ° C. can also be used. Since the super iodide formed during the reaction forms a molecular bond with the super fluoride, at least 2 moles of silver fluoride per mole of steroid must be present for a theoretical conversion. However, preference is given to using an excess of 10 to 500 liters, and more over this amount, in order to achieve higher yields. The silver fluoride is gradually added over a period of time. The reaction time is half an hour to six hours. To isolate the product, the solvent is evaporated and the crude product is extracted with a suitable solvent such as chloroform, methylene chloride, carbon tetrachloride, benzene or the like. The cleaning is carried out according to the usual methods, for. B. by further extraction to remove impurities, recrystallization or, if necessary, chromatographically.
Das erhaltene 6-Methyl-Ilß,17a-dio2iy#21-fluor-4-pregnen-3,20-dion kann in üblicher Weise mit Chromsäureanhydrid in Essigsäurelösung oder mit einem N-Halogenamid oder N-Halogenimid, wie N-Bromacetamid, N-Chlorsuccinimid, N-Bromsuccinimid od. dgl., in Pyridin, Dioxan oder anderen Lösungsmitteln zum 11-ketoDerivat oxydiert werden.The 6-methyl-ILß, 17a-dio2iy # 21-fluoro-4-pregnen-3,20-dione obtained can in the usual way with chromic anhydride in acetic acid solution or with a N-haloamide or N-haloimide, such as N-bromoacetamide, N-chlorosuccinimide, N-bromosuccinimide or the like, oxidized in pyridine, dioxane or other solvents to the 11-keto derivative will.
Das folgende Beispiel erläutert das erfmdungsgemäße Verfahren.The following example explains the method according to the invention.
Beispiel 6a-Methyl-Ilß,17a-dioxy-21-fluor-4-pregnen-3,20-dion Durch
Erhitzen bis zum Siedepunkt wurde eine Lösung von 1 g 6a-Methyl-Ilß,17a-dioxy-21-jod-4-pregnen-3,20-dion
in 150 ccm Acetonitril (technisch rein) hergestellt. Nach dem Kühlen auf
40'C wurde die Lösung vor Licht geschützt und unter Rühren 0,8 ccm einer
50 "/,igen wäßrigen Silberfluoridlösung zugegeben. Das Rühren wurde
1 Stunde bei etwa 40'C fortgesetzt. Dann wurden 0,7 ccm Süberfluoridlösung
und nach weiterem lstündigem Rühren nochmals 0,7 ccm wäßrige Silberfluoridlösung
zugegeben. Darauf wurde weitere 2 Stunden gerührt und erhitzt. Das braune Gernisch
wurde anschließend durch eine Schicht aus Diatomeenerde (bekannt unter dem Handelsnamen
Celite) filtriert und das Filtrat bei reduziertem Druck aus einem Bad bei einer
Temperatur von 50'C eingedampft. Der braune Rückstand wurde gründlich 2mal
mit je 100 ccm warmem Methylenchlorid extrahiert; die vereinigten Extrakte
wurden mit Wasser gewaschen, über wasserfreiem Natriumsulfat getrocknet und auf
ein Volumen von etwa 100 ccrn eingeengt und über 50 g synthetischem
Magnesiumsüikat (bekannt unter dem Handelsnamen Florisil) chromatographiert. Es
wurden auf die nachfolgende Weise Fraktionen von jeweils 200 ccm verwendet:
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1048274XA | 1956-09-10 | 1956-09-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1048274B true DE1048274B (en) | 1959-01-08 |
Family
ID=22302603
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEU4718A Pending DE1048274B (en) | 1956-09-10 | 1957-08-08 | Process for the preparation of 11,17ª ‡ -Dioxy-21-fluoro-4-pregnen-3,20-diones substituted in the 6-position by a hydrocarbon radical |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1048274B (en) |
-
1957
- 1957-08-08 DE DEU4718A patent/DE1048274B/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2649753C2 (en) | Processes and intermediates for the manufacture of steroids of the Pregnan range | |
| DE1048274B (en) | Process for the preparation of 11,17ª ‡ -Dioxy-21-fluoro-4-pregnen-3,20-diones substituted in the 6-position by a hydrocarbon radical | |
| DE2110140C3 (en) | ||
| DE1643017C3 (en) | Process for the preparation of e-chloro-1,2alpha-methylene-delta nor 4,6-pregnadienes | |
| DE1060394B (en) | Process for the manufacture of anti-inflammatory steroids | |
| EP0023713B1 (en) | 9-chloro-prednisolone derivatives, their preparation and their utilization | |
| DE1048914B (en) | Process for making steroid compounds | |
| DE935969C (en) | Process for the production of ª ‡, ª ‰ -unsaturated steroid ketones | |
| DE1593407C3 (en) | 17beta-Hydroxy-2-oxaestra-4,9 (10) dien-3-one and processes for the preparation of this compound | |
| DE2256866C3 (en) | Process for the preparation of 17 alpha- or 17beta-hydroxy compounds of the 20-ketopregnane or -17alpha-pregnane series | |
| DE1468988C (en) | Alpha-chloroethinyl-1-beta-ethyl-4-or-5 (10) -gon-3-ketone. ' | |
| DE1195747B (en) | Process for the production of new 16-methylene testosterone derivatives | |
| DE1593686C (en) | Method of making 3 Ketobenzo square bracket on d, square bracket add steroid | |
| DE1056605B (en) | Process for the preparation of steroids substituted in the 6-position by a hydrocarbon radical | |
| DE1048915B (en) | Process for the preparation of 6-methyl-9ª ‡, 21-difluoro-11ª ‰, 17ª ‡ -dioxy-1,4-pregnadiene-3,20-dione and its 11-keto analogues | |
| CH364777A (en) | Method of making steroids | |
| DE1058990B (en) | Process for the production of an anti-inflammatory steroid | |
| DE1169928B (en) | Process for the preparation of 21-bromo-5ª ‡ - or -5ª ‰ -pregnan-20-ones | |
| DE1145170B (en) | Process for the preparation of 9,11-oxidosteroids of the androstane and pregnane series | |
| DE1142362B (en) | Process for the preparation of enol acylates of 16ª ‡ -alkyl-20-ketosteroids of the pregnan and allopregnan series | |
| DE1046044B (en) | Process for the preparation of 11ª ‰, 17ª ‡ -Dioxy-21-fluoro-1,4-pregnadiene-3,20-dione and 17ª ‡ -oxy-21-fluoro-1,4-pregnadiene-3,11,20-trione | |
| DE1086229B (en) | Process for the preparation of therapeutically active steroid compounds | |
| DE1144723B (en) | Process for the preparation of 4, 6- (3 ', 1'-cyclopenteno) -? - pregnen- or -androstenverbindungen | |
| DE1079043B (en) | Process for the preparation of 6-alkyl- (or aryl) -11-oxy- (or keto) -17 ª ‡, 21-dioxy-4-pregnen-3, 20-diones and their 21-acylates | |
| DE1177150B (en) | Process for the preparation of 15-dehydro-16-methyl-17ª ‡ -fluoro-steroids of the pregnan series |