DE1106322B - Process for the preparation of 16-dehydro-16-phenyl -? - pregnen-3, 20-dione - Google Patents
Process for the preparation of 16-dehydro-16-phenyl -? - pregnen-3, 20-dioneInfo
- Publication number
- DE1106322B DE1106322B DEF28149A DEF0028149A DE1106322B DE 1106322 B DE1106322 B DE 1106322B DE F28149 A DEF28149 A DE F28149A DE F0028149 A DEF0028149 A DE F0028149A DE 1106322 B DE1106322 B DE 1106322B
- Authority
- DE
- Germany
- Prior art keywords
- phenyl
- pregnen
- dehydro
- dione
- diol
- 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 7
- 238000002360 preparation method Methods 0.000 title claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 7
- 230000008030 elimination Effects 0.000 claims description 4
- 238000003379 elimination reaction Methods 0.000 claims description 4
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 238000009835 boiling Methods 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000005977 Ethylene Substances 0.000 description 3
- ORNBQBCIOKFOEO-YQUGOWONSA-N Pregnenolone Natural products O=C(C)[C@@H]1[C@@]2(C)[C@H]([C@H]3[C@@H]([C@]4(C)C(=CC3)C[C@@H](O)CC4)CC2)CC1 ORNBQBCIOKFOEO-YQUGOWONSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- ORNBQBCIOKFOEO-QGVNFLHTSA-N pregnenolone Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 ORNBQBCIOKFOEO-QGVNFLHTSA-N 0.000 description 3
- 238000007127 saponification reaction Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- SMZOGRDCAXLAAR-UHFFFAOYSA-N aluminium isopropoxide Chemical compound [Al+3].CC(C)[O-].CC(C)[O-].CC(C)[O-] SMZOGRDCAXLAAR-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 230000003054 hormonal effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 241001000287 Helvetia Species 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 238000006036 Oppenauer oxidation reaction Methods 0.000 description 1
- -1 Phenyl alkali metal compounds Chemical class 0.000 description 1
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 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
- MUCRYNWJQNHDJH-OADIDDRXSA-N Ursonic acid Chemical compound C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C MUCRYNWJQNHDJH-OADIDDRXSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 231100000508 hormonal effect Toxicity 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- KSMWLICLECSXMI-UHFFFAOYSA-N sodium;benzene Chemical compound [Na+].C1=CC=[C-]C=C1 KSMWLICLECSXMI-UHFFFAOYSA-N 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- MYWQGROTKMBNKN-UHFFFAOYSA-N tributoxyalumane Chemical compound [Al+3].CCCC[O-].CCCC[O-].CCCC[O-] MYWQGROTKMBNKN-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
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 16-Dehydro-16-phenyl-44-pregnen-3,20-dion Es ist bereits bekannt, daB man aus 16-Dehydro-20-ketosteroiden durch Anlagerungsreaktionen zu 16-A1-kyl-20-ketosteroiden gelangen kann (vgl. Journal of the American Chemical Society, 64 [1942], S.1280, und Helvetia Chimica Acta, 27 [1944], S. 1803).Process for the preparation of 16-dehydro-16-phenyl-44-pregnen-3,20-dione It is already known that 16-dehydro-20-keto steroids can be obtained by addition reactions can reach 16-A1-kyl-20-ketosteroids (see Journal of the American Chemical Society, 64 [1942], p.1280, and Helvetia Chimica Acta, 27 [1944], p.1803).
Es wurde nun gefunden, daB man 16-Dehydro-16-phenyl-d 4-pregnen-3,20-dion erhält, wenn man in an sich bekannter Weise ein 3-Acyloxy-16,17-oxido-45-pregnen-20-on-20-ketal mit einer Phenyl-alkalimetall-Verbindung umsetzt, die erhaltenen 16-Phenyl-45-pregnen-3ß,17rx-diol-20-on-20-ketale in üblicher Weise entweder direkt oder über das entsprechende 16-Plienyl-d 5-pregnen-3ß,17a-diol-3,20-dion durch Hydrolyse und unter Wasserabspaltung in das 16-Dehydro-16-phenyl-45-pregnen-3ß-ol-20-on überführt und diese Verbindung in an sich bekannter Weise in 3-Stellung nach Oppenauer oxydiert.It has now been found that 16-dehydro-16-phenyl-d 4-pregnen-3,20-dione obtained when a 3-acyloxy-16,17-oxido-45-pregnen-20-one-20-ketal is obtained in a manner known per se reacts with a phenyl-alkali metal compound, the resulting 16-phenyl-45-pregnen-3ß, 17rx-diol-20-one-20-ketals in the usual way either directly or via the corresponding 16-plienyl-d 5-pregnen-3ß, 17a-diol-3,20-dione by hydrolysis and with elimination of water to 16-dehydro-16-phenyl-45-pregnen-3ß-ol-20-one and this compound in a known manner in the 3-position according to Oppenauer oxidized.
Die Umsetzung verläuft beispielsweise im Sinne des nachstehenden Formelschemas Als Ausgangsstoff für das Verfahren gemäß der Erfindung ist insbesondere das 20-Äthylenketal des 3-Acetoxy-16,17-oxido-45-pregnen-20-ons geeignet, das beispielsweise nach der in Journal of the American Chemical Society, 72 [1950], S.367, beschriebenen Methode hergestellt werden kann.The implementation takes place, for example, in the sense of the formula scheme below As a starting material for the process according to the invention, the 20-ethylene ketal of 3-acetoxy-16,17-oxido-45-pregnen-20-one is particularly suitable, which, for example, according to the in Journal of the American Chemical Society, 72 [1950] , P.367, described method can be produced.
Als Phenyl-alkalimetall-Verbindungen kommenPhenyllithium oder Phenylnatrium in Betracht.Phenyl alkali metal compounds are phenyl lithium or phenyl sodium into consideration.
Die in erster Umsetzungsstufe erfolgende Darstellung der 16-Phenyl-4 5-pregnen-3ß,17x-diol-20-on-20-ketale wird zweckmäßig bei Temperaturen zwischen -20 und +l00"C durchgeführt. Mit besonderem Vorteil sind Temperaturen um +40'C geeignet. Als Lösungsmittel kommen vor allem Benzol, Äther, Dioxan oder Tetrahydrofuran in Betracht. Besonders vorteilhaft ist- die Verwendung eines Gemisches aus Tetrahydrofuran und Äther (Diäthyläther).The preparation of 16-phenyl-4, which takes place in the first conversion stage 5-pregnen-3ß, 17x-diol-20-one-20-ketale is useful at temperatures between -20 and + 100 "C. Temperatures around + 40'C are particularly suitable. Benzene, ether, dioxane or tetrahydrofuran are the most common solvents Consideration. The use of a mixture of tetrahydrofuran is particularly advantageous and ether (diethyl ether).
Die in zweiter Umsetzungsstufe erfolgende saure Verseifung der erhaltenen 16-Phenyl-45-pregnen-3ß,17a-diol-20-on-20-ketale zum 16-Dehydro-16-phenyl-4 5-pregnen-3ß-ol-20-on wird vorteilhaft in alkoholischwäßriger Lösung durchgeführt, wobei als Alkohole alle mit Wasser mischbaren Verbindungen dieser Körperklasse in Betracht kommen. Vorteilhaft ist die Verwendung niedrigmolekularer Alkohole, wie Methanol, Äthanol oder Isopropanol.The acidic saponification of the obtained in the second reaction stage 16-Phenyl-45-pregnen-3ß, 17a-diol-20-one-20-ketals to 16-dehydro-16-phenyl-4 5-pregnen-3ß-ol-20-one is advantageously carried out in alcoholic aqueous solution, the alcohols all water-miscible compounds of this body class come into consideration. The use of low molecular weight alcohols such as methanol or ethanol is advantageous or isopropanol.
Als Säuren kommen anorganische Säuren, wie Salzsäure, Schwefelsäure oder Methansulfonsäure, und organische Säuren, wie p-Toluolsulfonsäure, in Betracht. Als besonders vorteilhaft hat sich die Verwendung von p-Toluolsulfonsäure in wäßrigem Methanol erwiesen. Als Lösungsmittel eignen sich niedrigmolekulare Alkohole, Dioxan oder Aceton. Die Reaktion wird vorzugsweise bei der jeweiligen Siedetemperatur des Lösungsmittels durchgeführt, wobei Temperaturen zwischen +40 und +100°C in Betracht kommen. Die Verseifung nimmt meist nur kurze Zeit in Anspruch; sie ist im allgemeinen innerhalb weniger Minuten beendet.Inorganic acids, such as hydrochloric acid and sulfuric acid, are used as acids or methanesulfonic acid, and organic acids, such as p-toluenesulfonic acid, into consideration. The use of p-toluenesulfonic acid in aqueous solution has proven to be particularly advantageous Proven methanol. Low molecular weight alcohols, dioxane, are suitable as solvents or acetone. The reaction is preferably carried out at the respective boiling point Solvent carried out, temperatures between +40 and + 100 ° C into consideration come. The saponification usually only takes a short time; she is in general finished within a few minutes.
Bei der sauren Verseifung des 16-Phenyl-4 5-pregnen-3ß,17x-diol-20-on-20-äthylenketals mit p-Toluolsulfonsäure in Methanol (vgl. Formelschema II bis IV) tritt zum größten Teil spontan Wasserabspaltung unter Bildung von 16-Dehydro-16-phenyl-45-pregnen-3ß-ol-20-on (IV) ein, während die entsprechende 16-Phenyl-17x-hydroxy-Verbindung (III) nur in geringer Menge entsteht. Letztere Verbindung, die sich aus dem Reaktionsgemisch isolieren läßt, geht bei längerer Einwirkung von Säure oder beim Umkristallisieren aus siedendem Eisessig ebenfalls unter Wasserabspaltung in die 16-Phenyl-16-dehydro-Verbindung (IV) über.In the acidic saponification of 16-phenyl-4 5-pregnen-3ß, 17x-diol-20-one-20-ethylene ketal with p-toluenesulfonic acid in methanol (cf. formula schemes II to IV) occurs to the greatest extent Partly spontaneous elimination of water with formation of 16-dehydro-16-phenyl-45-pregnen-3ß-ol-20-one (IV), while the corresponding 16-phenyl-17x-hydroxy compound (III) is only available in small amount arises. The latter compound that emerges from the reaction mixture can isolate, goes with prolonged exposure to acid or recrystallization from boiling glacial acetic acid, also with elimination of water, into the 16-phenyl-16-dehydro compound (IV) over.
In der dritten Reaktionsstufe wird das so erhaltene 16 - Dehydro -16 - phenyl -A5- pregnen - 3ß - o1- 20- an in 3-Stellung nach dem bekannten Oppenauer-Verfahren zu dem entsprechenden 3-Keton oxydiert. Hierbei setzt man die 3-Hydroxysteroide zweckmäßig in einem inerten Lösungsmittel, beispielsweise Benzol, Xylol oder vorteilhaft Toluol, mit einem Aluminiumalkoholat, z. B. Aluminiumisopropylat, -butylat, Aluminiumphenolat,und in Gegenwart von Ketonen, wie Aceton oder Cyclohexanon, um, wobei als Reaktionstemperaturen zweckmäßig die jeweiligen Siedetemperaturen der eingesetzten Lösungsmittel gewählt werden.In the third reaction stage, the 16-dehydro-16 obtained in this way - phenyl -A5- pregnen - 3ß - o1-20- an in the 3-position according to the known Oppenauer process oxidized to the corresponding 3-ketone. This is where the 3-hydroxysteroids are used expediently in an inert solvent, for example benzene, xylene, or advantageously Toluene, with an aluminum alcoholate, e.g. B. aluminum isopropylate, aluminum butylate, aluminum phenate, and in the presence of ketones, such as acetone or cyclohexanone, in order, with the reaction temperatures expediently chosen the particular boiling point of the solvents used will.
Die Oppenauer-Oxydation erfolgt .im allgemeinen sehr rasch und ist bei kleinen Ansätzen meistens nach etwa einer Stunde beendet.The Oppenauer oxidation generally takes place very quickly and is in the case of small batches usually ended after about an hour.
Das Verfahrenserzeugnis gemäß der vorliegenden Erfindung besitzt selbst Hormonwirkung oder stellt einen Ausgangsstoff zur Herstellung weiterer Folgeverbindungen mit Hormonwirkung dar.The process product according to the present invention has itself Hormone effect or provides a starting material for the production of further follow-up compounds with hormonal effects.
Die Verbindung kann als solche oder in Form von pharmazeutischen Zubereitungen, beispielsweise als ölige Suspensionen, als kristalline Suspensionen oder in Form von Lösungen bzw. Kapseln oder Tabletten, oral oder parenteral appliziert werden.The compound can be used as such or in the form of pharmaceutical preparations, for example as oily suspensions, as crystalline suspensions or in the form of solutions or capsules or tablets, orally or parenterally.
Beispiel a) 16-Dehydro-16-phenyl-45-pregnen-3ß-ol-20-on 54,9 g 3ß-Acetoxy-16,17-oxido-45-pregnen-20-on-20-äthylenketal werden in 790 ccm absolutem Tetrahydrofuran heiß gelöst und auf 25°C abgekühlt. Zu dieser Lösung wird unter Rühren und unter Stickstoff eine frisch bereitete ätherische Phenyl-lithium-Lösung (die aus 22,5 g Lithium, 157,5 ccm Brombenzol und 750 ccm Äther hergestellt wurde) unter Eiskühlung zugegeben. Hierbei steigt die Temperatur des Reaktionsgemisches auf 50°C an. Es wird auf Zimmertemperatur abgekühlt und noch 1 Stunde und 50 Minuten lang nachgerührt. Dann werden 3,91 Wasser eingerührt. Anschließend wird mit 750 ccm Äther extrahiert. Die organische Schicht wird mit Wasser neutral gewaschen, über Natriumsulfat getrocknet und unter vermindertem Druck bei einer Badtemperatur von 35°C zur Trockne eingedampft. Der Destillationsrückstand (rohes 16-Phenyl-45-pregnen-3ß,17a-diol-20-on 20-äthylenketal) wird in 1,81 Methanol gelöst und nach Versetzen mit einer Lösung von 92,4 g p-Toluolsulfonsäure in 255 ccm Wasser 45 Minuten lang unter Rückfluß und unter Stickstoff zum Sieden erhitzt. Anschließend wird abgekühlt und mit 1,351 Wasser versetzt. Nach einigem Stehen wird die auskristallisierte Substanz abgesaugt und mit einer Mischung aus Methanol und Wasser gewaschen. Der Filterrückstand wird aus Aceton umkristallisiert. Als erste Fraktion werden 28,9 g 16-Dehydro-16-phenyl-45-pregnen-3ß-ol-20-on vom Schmelzpunkt 216°C erhalten. Aus der Mutterlauge kann man nach weiterem Einengen noch 1,26 g 16-Phenyl-45-pregnen-3ß,17a-diol-20-on vom Schmelzpunkt 276°C isolieren. Letztere Verbindung geht beim Umkristallisieren aus wenig siedendem Eisessig in das 16-Dehydro-16-phenyl-4 5-pregnen-3ß-ol-20-on über. b) 16-Dehydro-16-phenyl-44-pregnen-3,20-dion 1,64 g 16-Dehydro-16-phenyl-A 5-pregnen-3ß-ol-20-on werden in 90 ccm Toluol heiß gelöst. Die Lösung wird mit 15 ccm frisch destilliertem Cyclohexanon versetzt. Von der Mischung werden dann 15 ccm Toluol abdestilliert und durch 15 ccm frisches Toluol ersetzt. Danach versetzt man das heiße Reaktionsgemisch mit einer Lösung von 2,1 g frisch destilliertem Aluminiumisopropylat in 15 ccm Toluol und erhitzt 55 Minuten lang unter Rückfluß zum Sieden. Zu dem noch heißen Reaktionsgemisch wird dann eine Lösung von 1 ccm Eisessig in 6 ccm Toluol eingerührt. Nach erschöpfender Wasserdampfdestillation wird der Rückstand im Vakuum zur Trockne eingeengt und anschließend mit heißem Aceton extrahiert. Beim Einengen des Acetonextraktes werden 1,08 g 16-Dehydro-16-phenyl-44-pregnen-3,20-dion vom Schmelzpunkt 207 bis 209°C erhalten.Example a) 16-Dehydro-16-phenyl-45-pregnen-3β-ol-20-one 54.9 g of 3β-acetoxy-16,17-oxido-45-pregnen-20-one-20-ethylene ketal are dissolved hot in 790 ccm of absolute tetrahydrofuran and cooled to 25 ° C. A freshly prepared essential solution is added to this solution while stirring and under nitrogen Phenyllithium solution (consisting of 22.5 g lithium, 157.5 ccm bromobenzene and 750 ccm Ether was prepared) was added while cooling with ice. This increases the temperature of the reaction mixture to 50 ° C. It is cooled to room temperature and still Stirred for 1 hour and 50 minutes. Then 3.91 of water are stirred in. Afterward is extracted with 750 cc of ether. The organic layer becomes neutral with water washed, dried over sodium sulfate and under reduced pressure at a Evaporated bath temperature of 35 ° C to dryness. The distillation residue (crude 16-Phenyl-45-pregnen-3ß, 17a-diol-20-one 20-ethyl ketal) is dissolved in 1.81 methanol and after adding a solution of 92.4 g of p-toluenesulfonic acid in 255 cc of water Heated to boiling under reflux and under nitrogen for 45 minutes. Afterward it is cooled and 1.351 water is added. After standing for a while, the crystallized Sucked off substance and washed with a mixture of methanol and water. Of the The filter residue is recrystallized from acetone. The first fraction will be 28.9 g of 16-dehydro-16-phenyl-45-pregnen-3β-ol-20-one with a melting point of 216 ° C. were obtained. the end After further concentration of the mother liquor, 1.26 g of 16-phenyl-45-pregnen-3β, 17a-diol-20-one can be added isolate from melting point 276 ° C. The latter connection goes with recrystallization from low-boiling glacial acetic acid into 16-dehydro-16-phenyl-4 5-pregnen-3ß-ol-20-one above. b) 16-Dehydro-16-phenyl-44-pregnen-3,20-dione 1.64 g of 16-dehydro-16-phenyl-A 5-pregnen-3ß-ol-20-one are dissolved in 90 cc of hot toluene. The answer is 15 ccm of freshly distilled cyclohexanone are added. The mix then becomes 15 cc of toluene distilled off and replaced by 15 cc of fresh toluene. Then moved the hot reaction mixture with a solution of 2.1 g of freshly distilled aluminum isopropylate in 15 cc of toluene and refluxed for 55 minutes. On top of that The hot reaction mixture then becomes a solution of 1 cc of glacial acetic acid in 6 cc of toluene stirred in. After exhaustive steam distillation, the residue is in vacuo concentrated to dryness and then extracted with hot acetone. When constricting of the acetone extract 1.08 g of 16-dehydro-16-phenyl-44-pregnen-3,20-dione from Melting point 207 to 209 ° C obtained.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF28149A DE1106322B (en) | 1959-04-09 | 1959-04-09 | Process for the preparation of 16-dehydro-16-phenyl -? - pregnen-3, 20-dione |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF28149A DE1106322B (en) | 1959-04-09 | 1959-04-09 | Process for the preparation of 16-dehydro-16-phenyl -? - pregnen-3, 20-dione |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1106322B true DE1106322B (en) | 1961-05-10 |
Family
ID=7092760
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEF28149A Pending DE1106322B (en) | 1959-04-09 | 1959-04-09 | Process for the preparation of 16-dehydro-16-phenyl -? - pregnen-3, 20-dione |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1106322B (en) |
-
1959
- 1959-04-09 DE DEF28149A patent/DE1106322B/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| None * |
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