CH207498A - Process for the preparation of a derivative of the 3-keto-cyclopentanopolyhydrophenanthrene series. - Google Patents
Process for the preparation of a derivative of the 3-keto-cyclopentanopolyhydrophenanthrene series.Info
- Publication number
- CH207498A CH207498A CH207498DA CH207498A CH 207498 A CH207498 A CH 207498A CH 207498D A CH207498D A CH 207498DA CH 207498 A CH207498 A CH 207498A
- Authority
- CH
- Switzerland
- Prior art keywords
- keto
- derivative
- preparation
- intermediate product
- series
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title claims description 3
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims description 10
- 239000013067 intermediate product Substances 0.000 claims description 5
- 229960003604 testosterone Drugs 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims description 3
- 150000003901 oxalic acid esters Chemical class 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 2
- 239000013078 crystal Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 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 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
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-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
- 239000002253 acid Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Landscapes
- 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
Verfahren zur Darstellung eines Derivates der 3-Keto-Cyclopentanopolyhydro- phonanthren-]Reihe. Es wurde gefunden, dass man zu einem Derivat der 3-Keto-Cyclopentanopolyhydro- phenanthren-Reihe gelangen kann, wenn man Testosteron mit einem Oxalsäureester um setzt, und hierauf auf das so erhaltene Zwi schenprodukt hydrolysierende Mittel einwir ken lässt.
Man erhält auf diese Weise den Testo- steroii-2-aldehyd der folgenden Formel:
EMI0001.0011
in Form farbloser Kristalle.
Die Umsetzung des Testosterons mit dem Oxalsäureester wird zweckmässig in Gegen wart geeigneter Kondensationsmittel ausge führt. Beispielsweise seien genannt: Alkali- metalle, wie Natrium, Kalium, Lithium, ins- besondere in Form ihrer Alkoholate, Amide und dergleichen. Zweckmässig arbeitet man hiebei auch in Gegenwart eines Lösungs mittels. Als solche kommen in Betracht zum Beispiel Benzol, Toluol, Hexan, Äther, Petrol- äther und dergleichen.
Oft ist es günstig die Umsetzung bei erhöhter Temperatur, ge gebenenfalls unter Druck auszuführen. Das so entstandene Zwischenprodukt ist ein 2- Ketocarbonsäureester, das' durch Behandeln mit hydrolysierenden Mitteln, zum Beispiel mit verdünnter Schwefelsäure bei erhöhter Temperatur, in den entsprechenden Aldehyd übergeführt wird.
Der Endstoff kann jeweils mittels physi kalischer Methoden, wie Umkristallisation, Destillation, Sublimation, Adsorption oder, unter Benützung seiner spezifischen reaktion- fähigen Gruppen, zum Beispiel über seine Kondensationsprodukte mit Carbonylreagen- tien gereinigt werden.
Die neue Verbindung soll therapeutische Verwendung finden oder als Zwischenprodukt zur Herstellung therapeutisch verwendbarer Stoffe dienen.
<I>Beispiel:</I> Zu einer Suspension von<B>0,7</B> Teilen trockenem Natriumäthylat in<B>50</B> Teilen ab solutem Benzol werden zuerst<B>1,5</B> Teile Oxal- säurediäthylester hinzgefügt, wobei das Äthylat in Lösung geht und hierauf<B>2,9</B> Teile Testosteron. Man erwärmt eine Stunde auf dem Wasserbade und lässt dann 2 Tage bei Zimmertemperatur stehen. Das Reaktionsge misch wird nunmehr mit Äther verdünnt und mit eiskaltem Wasser ausgesehüttelt. Die wässerige Lösung wird sofort unter Kühlung mit Essigsäure angesäuert und mehrmals mit Äther extrahiert.
Die vereinigten Ätheraus züge werden mit Wasser gewaschen, über wasserfreiem Natriumsulfat getrocknet und eingedarupft. Der so erhaltene Rückstand kann durch Umlösen aus Alkoholwasser, Essigester oder Xylol gereinigt werden. Der Testosteron-oxalyläthylester wird durch Be handeln mit verdünnter Schwefelsäure bei erhöhter Temperatur in den entsprechenden Testosteron-2-aldehyd überführt.
Process for the preparation of a derivative of the 3-keto-cyclopentanopolyhydrophonanthrene] series. It has been found that a derivative of the 3-keto-cyclopentanopolyhydrophenanthrene series can be obtained if testosterone is reacted with an oxalic acid ester and then hydrolyzing agents can act on the intermediate product thus obtained.
Testosteroii-2-aldehyde of the following formula is obtained in this way:
EMI0001.0011
in the form of colorless crystals.
The reaction of testosterone with the oxalic acid ester is expediently carried out in the presence of suitable condensing agents. Examples include: alkali metals, such as sodium, potassium, lithium, especially in the form of their alcoholates, amides and the like. It is also expedient to work in the presence of a solvent. Benzene, toluene, hexane, ether, petroleum ether and the like come into consideration as such.
It is often advantageous to carry out the reaction at elevated temperature, if necessary under pressure. The intermediate product thus formed is a 2-ketocarboxylic acid ester which is converted into the corresponding aldehyde by treatment with hydrolyzing agents, for example with dilute sulfuric acid at elevated temperature.
The end product can be purified using physical methods such as recrystallization, distillation, sublimation, adsorption or, using its specific reactive groups, for example via its condensation products with carbonyl reagents.
The new compound should find therapeutic use or serve as an intermediate product for the production of therapeutically useful substances.
<I> Example: </I> To a suspension of <B> 0.7 </B> parts of dry sodium ethylate in <B> 50 </B> parts of absolute benzene, <B> 1.5 </ B > Parts of diethyl oxalate added, the ethylate going into solution and then <B> 2.9 </B> parts of testosterone. It is heated on the water bath for one hour and then left to stand for 2 days at room temperature. The reaction mixture is now diluted with ether and shaken out with ice-cold water. The aqueous solution is immediately acidified with acetic acid while cooling and extracted several times with ether.
The combined ether extracts are washed with water, dried over anhydrous sodium sulfate and evaporated. The residue obtained in this way can be purified by dissolving it from alcohol water, ethyl acetate or xylene. The testosterone oxalylethyl ester is converted into the corresponding testosterone-2-aldehyde by loading with dilute sulfuric acid at an elevated temperature.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH207498T | 1937-07-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH207498A true CH207498A (en) | 1939-11-15 |
Family
ID=4445570
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH207498D CH207498A (en) | 1937-07-26 | 1937-07-26 | Process for the preparation of a derivative of the 3-keto-cyclopentanopolyhydrophenanthrene series. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH207498A (en) |
-
1937
- 1937-07-26 CH CH207498D patent/CH207498A/en unknown
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