CH214533A - Process for the preparation of a pregnen-5-ol-3-one-20 derivative. - Google Patents
Process for the preparation of a pregnen-5-ol-3-one-20 derivative.Info
- Publication number
- CH214533A CH214533A CH214533DA CH214533A CH 214533 A CH214533 A CH 214533A CH 214533D A CH214533D A CH 214533DA CH 214533 A CH214533 A CH 214533A
- Authority
- CH
- Switzerland
- Prior art keywords
- pregnen
- acetoxy
- diazomethane
- hydrogen chloride
- treated
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 claims description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 9
- 238000007127 saponification reaction Methods 0.000 claims description 5
- 239000007795 chemical reaction product Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- QRLVDLBMBULFAL-UHFFFAOYSA-N Digitonin Natural products CC1CCC2(OC1)OC3C(O)C4C5CCC6CC(OC7OC(CO)C(OC8OC(CO)C(O)C(OC9OCC(O)C(O)C9OC%10OC(CO)C(O)C(OC%11OC(CO)C(O)C(O)C%11O)C%10O)C8O)C(O)C7O)C(O)CC6(C)C5CCC4(C)C3C2C QRLVDLBMBULFAL-UHFFFAOYSA-N 0.000 claims description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 2
- UVYVLBIGDKGWPX-KUAJCENISA-N digitonin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O[C@H]5[C@@H]([C@@H](O)[C@@H](O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)CO7)O)[C@H](O)[C@@H](CO)O6)O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O7)O)[C@@H](O)[C@@H](CO)O6)O)[C@@H](CO)O5)O)C[C@@H]4CC[C@H]3[C@@H]2[C@@H]1O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 UVYVLBIGDKGWPX-KUAJCENISA-N 0.000 claims description 2
- UVYVLBIGDKGWPX-UHFFFAOYSA-N digitonine Natural products CC1C(C2(CCC3C4(C)CC(O)C(OC5C(C(O)C(OC6C(C(OC7C(C(O)C(O)CO7)O)C(O)C(CO)O6)OC6C(C(OC7C(C(O)C(O)C(CO)O7)O)C(O)C(CO)O6)O)C(CO)O5)O)CC4CCC3C2C2O)C)C2OC11CCC(C)CO1 UVYVLBIGDKGWPX-UHFFFAOYSA-N 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 238000002844 melting Methods 0.000 claims description 2
- 230000008018 melting Effects 0.000 claims description 2
- 229910052709 silver Inorganic materials 0.000 claims description 2
- 239000004332 silver Substances 0.000 claims description 2
- 239000003929 acidic solution Substances 0.000 claims 2
- 239000000243 solution Substances 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical group 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000003756 stirring Methods 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
- 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
-
- 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 eines Pregnen-ö-ol-3-on-20-Derlvates. Das Hauptpatent betrifft ein Verfahren zur Herstellung eines 21-Derivates des Pregnen- 5-ol-3-ons-20,nämlich des Acetoxy-21-pregnen- 5-ol-3-ons-20. Es wurde nun gefunden, dass man in analoger Weise auch solche Derivate des Pregnen-5-ol-3-ons-20 herstellen kann, die in 21-Stellung mit Halogen substituiert sind.
Diese in 21-Stellung mit Halogen substituier ten Derivate sind dadurch erhältlich, dass man die im Hauptpatent genannten 21-Diazo-deri- vate mit Halogenwasserstoff behandelt. So entsteht aus dem im Hauptpatent beschrie benen Acetoxy-3-diazo-21-pregnen-5-on-20 durch Einwirkung von Chlorwasserstoff das Acetoxy-3-chlor-21-pregnen-5-on-20, welches durch Verseifung in Chlor-21-pregnen-5-ol-3- on-20 übergeführt werden kann.
Die Reihen folge von Behandlung mit HCl und Verseifung ist für die Erfindung bedeutungslos, das heisst man kann aus dem Acetoxy-3-diazo-21-pregnen- 5-on-20 zuerst das Diazo-21-pregnen-5-ol-3- on-20 herstellen und dies mit Chlorwasserstoff behandeln oder umgekehrt.
Auch ist es gleichgültig, ob man die zwei Stufen der Überführung des Acyloxy-3-ätio- cholensäurechlorids in das Chlor-21-acyloxy-3- pregnen-5-on-20 in einem oder in zwei Reak tionsgängen ausführt.
Wird das Diazomethan nur allmählich in kleinen Mengen dem Säurechlorid zugesetzt, so wird das zuerst entstandene Diazo-21-acyl- oxy-3-pregnen-5 sofort durch die frei werdende Chlorwasserstoffsäure in das Chlor-21-acyloxy- 3-pregnen-5-on-20 umgesetzt.
Setzt man da gegen dem Diazomethan (mindestens 2 Mol) nach und nach das Säurechlorid (1 Mol) zu, so wirkt die frei werdende Chlorwasserstoff- säure auf das überschüssige Diazomethan ein unter Bildung von Methylchlorid und Stick stoffentwicklung. Das Diazo-21-acyloxy-3- pregnen-5-ol-3 wird so nicht angegriffen.
Durch nachträgliche Einwirkung von Ohlorwasser- stoff wird das Diazo-21-acyloxy-3-pregnen-5- on-20 in das Chlor-21-acyloxy-3-pregnen-5-on- 20 umgesetzt.
Durch Verseifung entsteht das Chlor-21- pregnen-5-ol-3-on-20.
Das den Gegenstand des vorliegenden Pa tentes bildende Verfahren ist dadurch gekenn zeichnet, dass man Acyloxy- 3 - ätiocholen- 5 - säure in das entsprechende Säurehalogenid überführt, dieses mit Diazomethan behandelt und das Reaktionsprodukt einer Behandlung mit Chlorwasserstoff und einer Verseifung in beliebiger Reihenfolge unterwirft.
<I>Beispiele:</I> 1. 0,2 g des wie im Hauptpatent be schrieben hergestellten Acetoxy-3-diazo-21- pregnen-5-ons-20 werden in Äther suspendiert oder gelöst und mit ätherischer trockener Chlor wasserstoffsäure versetzt, bis die stürmische Gasentwicklung beendet ist.
Hierauf dampft man den Äther und allfälligen überschüssigen Chlorwasserstoff im Vakuum vollständig weg und kristallisiert aus Äther unter Zusatz von Petroläther, dann aus Alkohol, wobei das Acetoxy-3-chlor-21-pregnen-5-on-20 in farb losen Nadeln vom Smp. 157-158 (korr.) und der Zusammensetzung C1sHss0aC1 erhal ten wird. Die Ausbeute beträgt 0,15 g rein stes Produkt.
Dasselbe Produkt wird erhalten, wenn man zu einer ätherischen Lösung von Acetoxy-3-ätiocholen-5-säurechloi@id bei Zim mertemperatur langsam, zweckmässig unter Rühren, Diazomethanlösung zutropfen lässt.
0,1 g des Acetoxy-3-chlor-21-pregnen-5- on-3 wird mit 2 ein-' Alkohol unter Zusatz von 0,15 em3 konzentrierter wässriger Salz säure 1 Stunde unter Rückfluss gekocht, im Vakuum eingedampft und aus Äther-Petrol- äther oder wenig Alkohol umkristallisiert. Aus letzterem werden farblose Nadeln vom Smp. 162-1641 (korr.) enthalten ;
sie zeigen die Zusammensetzung CziHs,0-.Cl. Die Verbindung ist mit Digitonin fällbar und reduziert alka lische Silberlösung rasch in der Kälte.
2. 1 g des wie im Hauptpatent beschrieben hergestellten Acetoxy-3-diazo-21-pregnen-5- ons-20 wird in der ebenfalls dort beschriebenen Weise in alkoholischer Lauge verseift zu dem Diazo-21-pregnen-5-ol-3-on-20. Dieses wird nun analog wie in Beispiel 1 mit Chlorwasserstoff behandelt, wobei man sofort das Chlor-21- pregnen-5-ol-3-on-20 gewinnt.
Process for the preparation of a pregnen-ö-ol-3-one-20 derivative. The main patent relates to a process for the preparation of a 21-derivative of pregnen-5-ol-3-one-20, namely acetoxy-21-pregnen-5-ol-3-one-20. It has now been found that derivatives of pregnen-5-ol-3-one-20 which are substituted by halogen in the 21-position can also be prepared in an analogous manner.
These derivatives substituted by halogen in the 21-position can be obtained by treating the 21-diazo derivatives mentioned in the main patent with hydrogen halide. Acetoxy-3-chloro-21-pregnen-5-one-20 is formed from the acetoxy-3-diazo-21-pregnen-5-one-20 described in the main patent by the action of hydrogen chloride, which is produced by saponification in chlorine. 21-pregnen-5-ol-3-one-20 can be converted.
The sequence of treatment with HCl and saponification is meaningless for the invention, that is, one can first get the diazo-21-pregnen-5-ol-3- from the acetoxy-3-diazo-21-pregnen-5-one-20 Make on-20 and treat it with hydrogen chloride or vice versa.
It also makes no difference whether the two stages of converting the acyloxy-3-ethio-cholenic acid chloride into the chloro-21-acyloxy-3-pregnen-5-one-20 are carried out in one or in two reactions.
If the diazomethane is only gradually added to the acid chloride in small amounts, the diazo-21-acyl-oxy-3-pregnen-5 formed first is immediately converted into chloro-21-acyloxy-3-pregnen-5- by the hydrochloric acid released. implemented on-20.
If the acid chloride (1 mol) is gradually added against the diazomethane (at least 2 mol), the released hydrochloric acid acts on the excess diazomethane with the formation of methyl chloride and nitrogen development. The diazo-21-acyloxy-3-pregnen-5-ol-3 is not attacked in this way.
Subsequent action of hydrochloric acid converts the diazo-21-acyloxy-3-pregnen-5-one-20 into the chlorine-21-acyloxy-3-pregnen-5-one-20.
The chlorine-21-pregnen-5-ol-3-one-20 is formed by saponification.
The process forming the subject of the present patent is characterized in that acyloxy 3-etiocholenic acid is converted into the corresponding acid halide, this is treated with diazomethane and the reaction product is subjected to treatment with hydrogen chloride and saponification in any order.
<I> Examples: </I> 1. 0.2 g of the acetoxy-3-diazo-21-pregnen-5-ons-20 produced as described in the main patent are suspended or dissolved in ether and mixed with ethereal dry hydrochloric acid until the stormy evolution of gas has ended.
The ether and any excess hydrogen chloride are then completely evaporated in vacuo and crystallized from ether with the addition of petroleum ether, then from alcohol, with the acetoxy-3-chloro-21-pregnen-5-one-20 in colorless needles of mp. 157-158 (corr.) And the composition C1sHss0aC1 is obtained. The yield is 0.15 g of the purest product.
The same product is obtained when diazomethane solution is slowly added dropwise to an ethereal solution of acetoxy-3-ätiocholen-5-säurechloi @ id at room temperature, conveniently with stirring.
0.1 g of acetoxy-3-chloro-21-pregnen-5-one-3 is refluxed for 1 hour with 2 one 'alcohol with the addition of 0.15 em3 concentrated aqueous hydrochloric acid, evaporated in vacuo and removed from ether -Petrol- ether or a little alcohol recrystallized. The latter contain colorless needles with a melting point of 162-1641 (corr.);
they show the composition CziHs, 0-.Cl. The compound can be precipitated with digitonin and quickly reduces alkaline silver solution in the cold.
2. 1 g of the acetoxy-3-diazo-21-pregnen-5-ons-20 prepared as described in the main patent is saponified in alcoholic liquor in the manner also described there to give the diazo-21-pregnen-5-ol-3- on-20. This is then treated with hydrogen chloride analogously to Example 1, the chlorine-21-pregnen-5-ol-3-one-20 being obtained immediately.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH204844T | 1937-03-22 | ||
| CH214533T | 1937-03-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH214533A true CH214533A (en) | 1941-04-30 |
Family
ID=25724080
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH214533D CH214533A (en) | 1937-03-22 | 1937-03-22 | Process for the preparation of a pregnen-5-ol-3-one-20 derivative. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH214533A (en) |
-
1937
- 1937-03-22 CH CH214533D patent/CH214533A/en unknown
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