CH211772A - Process for the preparation of an acid of the cyclopentanopolyhydrophenanthrene series. - Google Patents
Process for the preparation of an acid of the cyclopentanopolyhydrophenanthrene series.Info
- Publication number
- CH211772A CH211772A CH211772DA CH211772A CH 211772 A CH211772 A CH 211772A CH 211772D A CH211772D A CH 211772DA CH 211772 A CH211772 A CH 211772A
- Authority
- CH
- Switzerland
- Prior art keywords
- acid
- preparation
- forms
- metal
- acid ester
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims description 11
- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 4
- QGXBDMJGAMFCBF-HLUDHZFRSA-N 5α-Androsterone Chemical compound C1[C@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC[C@H]21 QGXBDMJGAMFCBF-HLUDHZFRSA-N 0.000 claims description 4
- QGXBDMJGAMFCBF-UHFFFAOYSA-N Etiocholanolone Natural products C1C(O)CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC21 QGXBDMJGAMFCBF-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 229940061641 androsterone Drugs 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000013078 crystal Substances 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 238000002844 melting Methods 0.000 claims description 3
- 230000008018 melting Effects 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- 239000011701 zinc Substances 0.000 claims description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 150000001875 compounds Chemical group 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- 238000007127 saponification reaction Methods 0.000 claims description 2
- -1 alkyl compound Chemical class 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-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
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- ZVHNNCSUTNWKFC-UHFFFAOYSA-N 4-(9h-fluoren-9-ylmethoxycarbonyl)-1-[(2-methylpropan-2-yl)oxycarbonyl]piperazine-2-carboxylic acid Chemical compound C1C(C(O)=O)N(C(=O)OC(C)(C)C)CCN1C(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 ZVHNNCSUTNWKFC-UHFFFAOYSA-N 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- FDCINQSOYQUNKB-UHFFFAOYSA-N UNPD98205 Natural products C1CC2C3(C)CCC(OC(=O)C)CC3CCC2C2CCC(=O)C21C FDCINQSOYQUNKB-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
-
- 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)
Description
Verfahren zur Herstellung einer Säure der Cyelopentanopolyhydrophenanthren-Reihe. Gegenstand des vorliegenden Patentes ist ein Verfahren zur Herstellung von 3.17- Dioxy-a.ndrostanyl-17-propionsäure, das da durch gekennzeichnet ist, dass man auf An- drosteron unter intermediärem Schutz der Hydroxylgruppe in Gegenwart eines Metalles, das fähig ist Alkylverbindungen zu bilden,
einen a-Halogenpropionsäureester einwirken lässt und den nach Zersetzung des so erhal tenen Reaktionsproduktes mittels Säure ge bildeten Oxysäureester mit einem verseifen- den Mittel behandelt.
Die Verseifung wird zweckmässigerweise mit alkalischen Mitteln durchgeführt. Als Metall, das fähig ist Alkylverbindungen zu bilden, verwendet man vorteilhaft Zink oder Magnesium.
Die neue Verbindung soll als Zwischen produkt für die Herstellung hormonwirk samer Substanzen Verwendung finden.
Beispiel <I>1:</I> 10 g Androsteron werden zum Schutz der Hy droxylgruppe in das Androsteronacetat übergeführt und letzteres in 200 cm' trocke nem Benzol gelöst und darauf 2 g gekörnten Zinks und 5 g a-Brompropionsäureäthylester zugefügt. Zur Einleitung der Reaktion wird ein kleiner Kristall Jod zugefügt und die Mischung auf dem Wasserbad etwa 5 Stun den erhitzt. Die Reaktionsmischung wird mit verdünnter Schwefelsäure zersetzt, darauf mit Wasser und Sodalösung und wiederum mit Wasser gewaschen und das Benzol ver jagt.
Der ölige Rückstand kristallisiert nach längerem Stehen; er wird mit alkoholischem Alkali behandelt und vorsichtig 2 Stunden lang auf dem Wasserbad erwärmt. Dann wird mit Wasser verdünnt und die Lösung im Eis schrank stehen gelassen. Das nicht in Re aktion getretene .Ausgangsmaterial kristalli siert hierbei aus und kann abfiltriert werden. Die Lösung enthält das Natriumsalz der neuen Säure, welches sich leicht aussalzen lässt, nachdem der Alkohol abgedampft und ein etwa gleiches Volumen gesättigter Koch salzlösung zugefügt worden ist.
Das abfil- trierte Salz wird wiederum durch Erwärmen mit Wasser gelöst und nochmals ausgesalzen. Es wird dann mit Äther und Salzsäure durch geschüttelt, wobei die freie Säure in dem Äther sich auflöst. Der Äther wird abge dampft, die kristallisierende Substanz in Aceton in einem grösseren Betrag als zur Lösung notwendig ist aufgelöst und darauf Wasser zugefügt, bis die Lösung trübe wird. Nach einigem Stehen im Eisschrank scheiden sich schöne Kristalle aus, die einen Schmelz punkt von 238-240 zeigen.
Der Reaktions verlauf lässt sich in folgender Weise an deuten:
EMI0002.0003
Die Reaktion kann auch ohne Zufügung von Benzol ausgeführt werden, jedoch ver schlechtern sich dann die Ausbeuten.
<I>Beispiel 2:</I> 10 g Androsteron werden in<B>100</B> cm' ab solutem Dibutyläther gelöst und 3 g Magne- sium-Metall, wie es für Grignard-Reaktionen gebraucht wird, zugefügt. Dann setzt man 5 g a-Brompropionsäure-äthylester hinzu und erwärmt die Mischung, nachdem ein kleiner Kristall Jod zugegeben wurde, etwa 5 Stun den.
Die Reaktionsmischung wird dann auf gearbeitet wie im Beispiel 1 beschrieben. Die erhaltene Säure kann aus Aceton oder Al kohol und Wasser umkristallisiert werden. Ihr Schmelzpunkt liegt bei etwa. 240'.
Process for the preparation of an acid of the cyelopentano polyhydrophenanthrene series. The subject of the present patent is a process for the preparation of 3.17-Dioxy-a.ndrostanyl-17-propionic acid, which is characterized by the fact that one on androsterone with intermediate protection of the hydroxyl group in the presence of a metal capable of forming alkyl compounds ,
an α-halopropionic acid ester is allowed to act and the oxy acid ester formed after the decomposition of the reaction product obtained by means of acid is treated with a saponifying agent.
The saponification is expediently carried out with alkaline agents. The metal that is capable of forming alkyl compounds is advantageously zinc or magnesium.
The new compound is intended to be used as an intermediate product for the manufacture of substances with hormone effects.
Example <I> 1: </I> 10 g of androsterone are converted into androsterone acetate to protect the hydroxyl group and the latter is dissolved in 200 cm 'of dry benzene and then 2 g of granulated zinc and 5 g of ethyl α-bromopropionate are added. To initiate the reaction, a small crystal of iodine is added and the mixture is heated on the water bath for about 5 hours. The reaction mixture is decomposed with dilute sulfuric acid, then washed with water and soda solution and again with water and the benzene is chased away.
The oily residue crystallizes after prolonged standing; it is treated with alcoholic alkali and carefully heated on the water bath for 2 hours. It is then diluted with water and the solution is left to stand in the ice cabinet. The starting material that has not reacted crystallizes out and can be filtered off. The solution contains the sodium salt of the new acid, which can easily be salted out after the alcohol has evaporated and an approximately equal volume of saturated saline solution has been added.
The filtered salt is again dissolved by heating with water and salted out again. It is then shaken through with ether and hydrochloric acid, whereby the free acid in the ether dissolves. The ether is evaporated, the crystallizing substance is dissolved in acetone in a larger amount than is necessary for the solution and then water is added until the solution becomes cloudy. After standing in the refrigerator for a while, beautiful crystals separate with a melting point of 238-240.
The course of the reaction can be indicated in the following way:
EMI0002.0003
The reaction can also be carried out without adding benzene, but the yields then deteriorate.
<I> Example 2: </I> 10 g of androsterone are dissolved in <B> 100 </B> cm 'from solute dibutyl ether and 3 g of magnesium metal, as needed for Grignard reactions, are added. Then 5 g of a-bromopropionic acid ethyl ester are added and the mixture is heated for about 5 hours after a small crystal of iodine has been added.
The reaction mixture is then worked up as described in Example 1. The acid obtained can be recrystallized from acetone or alcohol and water. Their melting point is around. 240 '.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US211772XA | 1936-06-22 | 1936-06-22 | |
| CH202242T | 1937-06-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH211772A true CH211772A (en) | 1940-10-15 |
Family
ID=25723775
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH211772D CH211772A (en) | 1936-06-22 | 1937-06-21 | Process for the preparation of an acid of the cyclopentanopolyhydrophenanthrene series. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH211772A (en) |
-
1937
- 1937-06-21 CH CH211772D patent/CH211772A/en unknown
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