CH205522A - Process for the preparation of a 20-ketone of the cyclopentanopolyhydrophenanthrene series. - Google Patents
Process for the preparation of a 20-ketone of the cyclopentanopolyhydrophenanthrene series.Info
- Publication number
- CH205522A CH205522A CH205522DA CH205522A CH 205522 A CH205522 A CH 205522A CH 205522D A CH205522D A CH 205522DA CH 205522 A CH205522 A CH 205522A
- Authority
- CH
- Switzerland
- Prior art keywords
- ketone
- preparation
- condensation
- carbon dioxide
- series
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 9
- 238000002360 preparation method Methods 0.000 title description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 5
- 239000001569 carbon dioxide Substances 0.000 claims description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 4
- 238000009833 condensation Methods 0.000 claims description 4
- 230000005494 condensation Effects 0.000 claims description 4
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 150000002168 ethanoic acid esters Chemical class 0.000 claims description 2
- 238000007127 saponification reaction Methods 0.000 claims description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims 1
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 150000001340 alkali metals Chemical class 0.000 claims 1
- 230000008030 elimination Effects 0.000 claims 1
- 238000003379 elimination reaction Methods 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 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
- 239000003513 alkali Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000007859 condensation product Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000003786 synthesis reaction 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
- 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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Verfahren zur Herstellung eines 20-Hetons der Cyclopentanopolyhydrophenanthrenreihe. Es wurde gefunden, dass man gesättigte und ungesättigte Ketone der Cyclopentano- polyhydrophenanthrenreihe mit mindestens einer Ketogruppe in 20-Stellung erhalten kann, wenn man gesättigte oder ungesät tigte Derivate der Ätiocholan- oder Ätio- allo-cholansäure, die im Ringsystem noch Substituenten,
insbesondere Sauerstoff ent halten können, in an sich bekannter Weise, durch Kondensation mit solchen Carbonsäu- ren oder P-Di-carbonsäuren oder Derivaten derselben, wie Estern, Amiden, Nitrilen usw., die noch mindestens ein Wasserstoffatom neben der Carboxylgruppe enthalten, in a-Ke- tonsKurederivate überführt, und diese gegebe nenfalls nach weiterer Umsetzung einer Ver- seifung und Decarboxylierung unterzieht.
Die Produkte sollen zur Herstellung pharma zeutisch wertvoller Präparate oder als Zwi schenprodukte für die Bereitung von solchen verwendet werden.
Als Derivate der Ätiocholan- oder Ätio- allo-cholansäure können hier die Ester dieser Säuren genannt werden. Die Kondensation mit Verbindungen der allgemeinen Form
EMI0001.0028
in welcher Ri und R2, Wasserstoff, Alkyl, Acyloxyl, Alkoxyl oder verestertes Carboxyl vorstellen und R = Alkyl, findet statt unter Einfluss von Alkali- oder Erdalkalimetallen.
Das vorliegende Patent bezieht sich auf ein Verfahren zur Herstellung des bekannten Pregnen-5-ol-3-on-20, das dadurch gekenn zeichnet ist, dass man einen Hydroxy-3-ätio- cholen-5-carbonsäureester mit einem Essig säureester unter Verwendung eines Alkali- oder Erdalkalimetalles kondensiert, das Konden sationsprodukt verseift und aus der so er haltenen Säure Kohlendioxyd abspaltet. Die Kohlendioxydabspaltung kann durch Erhitzung der Säure im Vakuum, z. B. unter Zusatz von basischen Mitteln erfolgen.
Der Hergang der Synthese wird durch folgende Formeln erläutert
EMI0002.0001
<I>Beispiel:</I> 3-Oxy-ätiochol-5-en-säure (Smp. 285 kor, unter Zersetzung) wird in üblicher Weise in den Methylester übergeführt, der aus Metha nol in Nadeln vom Smp. 180 kor. kristalli siert. 1 g dieses Esters wird mit 1 g Essig- säureäthylester vermischt und mit 0,2 g fein zerschnittenem Natrium versetzt, 24 Stunden bei Zim@ilertet@@pera'tur stebengelassen, wor auf das Natrium zerfallen und ein gelber Brei entstanden ist. Man zerlegt mit Eis und Säure.
Nach längerem Schütteln wird abgetrennt und ausgeäthert. Die Ätherlösung wird mit Wasser gewaschen, getrocknet und vom Äther befreit. Das rohe Kondensations produkt wird verseift durch 12-stündiges Kochen mit stark verdünnter Natronlauge unter Zusatz von Alkohol. Die im Äther verbleibenden Neutralteile geben nach De stillation im Hochvakuum und Umkristalli- sieren aus Toluol das bekannte Pregrr-5-en- 3-ol-20-on vom Smp. 190 . Aus den sauren Anteilen gewinnt man einen Teil der Aus gangssäure zurück.
Das erhaltene, mit dein bekannten Produkt identische Pregnen-5-ol- 3-on-20 soll als Arzneimittel oder als Zwi schenprodukt für die Herstellung von Arznei mitteln Verwendung finden.
Process for the preparation of a 20-hetone of the cyclopentanopolyhydrophenanthrene series. It has been found that saturated and unsaturated ketones of the cyclopentano polyhydrophenanthrene series with at least one keto group in the 20-position can be obtained if saturated or unsaturated derivatives of etiocholanic or etioallo-cholanic acid, which still have substituents in the ring system,
in particular oxygen can contain, in a manner known per se, by condensation with such carboxylic acids or P-dicarboxylic acids or derivatives thereof, such as esters, amides, nitriles, etc., which also contain at least one hydrogen atom in addition to the carboxyl group, in a -KetonsKurederivate transferred, and these, if necessary, subjected to saponification and decarboxylation after further conversion.
The products should be used for the manufacture of pharmaceutically valuable preparations or as inter mediate products for the preparation of such.
The esters of these acids may be mentioned here as derivatives of etiocholanic or etioallo-cholanic acid. The condensation with compounds of the general form
EMI0001.0028
in which Ri and R2 represent hydrogen, alkyl, acyloxyl, alkoxyl or esterified carboxyl and R = alkyl, takes place under the influence of alkali or alkaline earth metals.
The present patent relates to a process for the preparation of the known pregnen-5-ol-3-one-20, which is characterized in that a hydroxy-3-ethio-cholen-5-carboxylic acid ester is used with an acetic acid ester of an alkali or alkaline earth metal condenses, saponifies the condensation product and splits off carbon dioxide from the acid thus obtained. The carbon dioxide can be split off by heating the acid in vacuo, e.g. B. be done with the addition of basic agents.
The synthesis process is illustrated by the following formulas
EMI0002.0001
<I> Example: </I> 3-Oxy-etiochol-5-en-acid (melting point 285 cor, with decomposition) is converted in the usual way into the methyl ester, which is obtained from methanol in needles of melting point 180 cor. crystallizes. 1 g of this ester is mixed with 1 g of ethyl acetate and mixed with 0.2 g of finely chopped sodium, left to stand for 24 hours at Zim @ iletzt @@ pera'tur, whereupon the sodium disintegrates and a yellow paste is formed. One decomposes with ice and acid.
After prolonged shaking, it is separated off and extracted with ether. The ether solution is washed with water, dried and freed from ether. The crude condensation product is saponified by boiling for 12 hours with highly dilute sodium hydroxide solution with the addition of alcohol. The neutral parts remaining in the ether give, after distillation in a high vacuum and recrystallization from toluene, the known Pregrr-5-en-3-ol-20-one with a melting point of 190. Part of the acid is recovered from the acidic components.
The obtained, identical with your known product Pregnen-5-ol-3-one-20 should be used as a drug or as an inter mediate product for the manufacture of drugs.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH205522T | 1937-07-25 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH205522A true CH205522A (en) | 1939-06-30 |
Family
ID=4444657
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH205522D CH205522A (en) | 1937-07-25 | 1937-07-25 | Process for the preparation of a 20-ketone of the cyclopentanopolyhydrophenanthrene series. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH205522A (en) |
-
1937
- 1937-07-25 CH CH205522D patent/CH205522A/en unknown
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