CH296566A - Process for the preparation of a 17-methylpregnene compound. - Google Patents
Process for the preparation of a 17-methylpregnene compound.Info
- Publication number
- CH296566A CH296566A CH296566DA CH296566A CH 296566 A CH296566 A CH 296566A CH 296566D A CH296566D A CH 296566DA CH 296566 A CH296566 A CH 296566A
- Authority
- CH
- Switzerland
- Prior art keywords
- methyl
- compound
- methylpregnene
- etio
- preparation
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 8
- -1 17-methylpregnene compound Chemical class 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title description 2
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229940126601 medicinal product Drugs 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 239000012362 glacial acetic acid Substances 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
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- YKYOUMDCQGMQQO-UHFFFAOYSA-L cadmium dichloride Chemical compound Cl[Cd]Cl YKYOUMDCQGMQQO-UHFFFAOYSA-L 0.000 description 2
- VQNPSCRXHSIJTH-UHFFFAOYSA-N cadmium(2+);carbanide Chemical compound [CH3-].[CH3-].[Cd+2] VQNPSCRXHSIJTH-UHFFFAOYSA-N 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 241000523878 Pseudarthrobacter equi Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000007256 debromination reaction Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc 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
- 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)
- Steroid Compounds (AREA)
Description
Verfahren zur Herstellung einer 17-Methylpregnenverbindung. Es wurde gefunden, dass man zu einer neuen 17-Methylpregnenverbindung gelangen kann, wenn man ein 44-3-Oxo-17a-methyl- ätio-chlolensäurehalogenid mit einer Methyl- Metallverbindimg reagieren lässt.
Das neue Verfahrensprodukt, das .d 4-17a- Methyl-3,20-dioxo-pregnen (17a-Methylprog- esteron) vom F. = 129 bis 130 ist progesta- tiv hochwirksam. Es soll als Heilmittel oder als Zwiselienprodukt zur Herstellung von Heilmitteln Verwendung finden.
Bei der verfahrensgemässen Unisetzung verwendet man als Methvl-lIetallverbind-Lui- gen zum Beispiel eine solche des Magnesiums, Kadmiums oder Zinks.
Beispiel.: 1. Gewichtsteil d 4-17a-Methyl-3-oxo-ätio- cholensäurechlorid, gelöst. in 30 Voluinteilen Xther, wird tropfenweise mit einer Lösung von Dimethylcadmium (bereitet in üblicher Weise aus 7,6 Gewichtsteilen Magnesiumspä- nen, 30 Volumteilen Äther, 10 Gewichtsteilen Methylbromid und 9 Gewichtsteilen Cad- miumehlorid) in Äther versetzt.
Das Reak- tionsgemisch wird anschliessend zwei Stunden unter Rühren zum Sieden erhitzt, dann vor sichtig mit Wasser zersetzt und schliesslich mit Äther extrahiert. Die übliche Aufarbei tung des ätherischen Auszuges liefert 0,9 Ge wichtsteile rohes 17a-Methyl-progesteron der Formel
EMI0001.0037
welches nach dein 1Jmkristallisieren aus Äther Petroläther bei 129 bis 130 schmilzt; [a] D _ -I- 113 (in Chloroform).
Das als Ausgangsmaterial verwendete d 4-17a-Methyl-3-oxo-ätio - cholensäure- chlorid kann aus der bekannten d 5-17a-Methyl-3-ss- oxy-ätio-ehlolensäure auf folgendem Wege be reitet werden:
Die Oxy-säure wird in Eisessig-Lösung unter Zusatz von Natriumaeetat mit 1 Mol Brom behandelt, das erhaltene rohe 5,6-Di bromid mit Chrointrioxy d in Eisessig-Lösung oxydiert, und schliesslich wird ohne Isolierung von Zwischenstufen eine Entbromung mit Zinkstaub in Eisessig vorgenommen.
Aus 1 Ge wichtsteil J5-17a-Metliyl-3ss-oxy-ätio-eholen- säure erhält man nach dem L:mkristallisieren des Rohproduktes aus Aceton 0,8 Gewichts teile d 4-17a-Methyl-3-oxo-ätio-cholensäure, die bei 291 bis 293 schmilzt:
[a] D = -I-89 (in Dioxan). Zur Bereitung des Säureclflorids wird die d 4-17a-Methyl-3-oxo-ätio-eholensä-LLive in Äthanol aufgenommen, mit einem.
Äqui valent 0,1n-Natronlauge versetzt, die Lösung zur Trockne eingedampft und schliesslich das erhaltene Natriumsalz im Hochvakuum bei 120 getroeknet. Das Natriumsalz wird an schliessend in absolutem Benzol aufgeschlemmt und nach Zusatz von wenig Pyridin mit Oxaly lchlorid versetzt. Die Reaktion ist nach 30 :Minuten beendet, worauf die Lösung zur Trockne eingedampft wird.
Das rohe Säure- ehlorid wird in Äther aufgenommen, die Lö sung vom ausgeschiedenen N atriumehlorid ab filtriert und direkt in der oben beschriebenen Weise mit Dimethylcadmium umgesetzt.
Process for the preparation of a 17-methylpregnene compound. It has been found that a new 17-methylpregnene compound can be obtained if a 44-3-oxo-17a-methyl-etio-chlolenic acid halide is allowed to react with a methyl metal compound.
The new process product, the .d 4-17a-methyl-3,20-dioxo-pregnen (17a-methylprogesterone) from F. = 129 to 130, is highly progestationally effective. It should be used as a remedy or as an intermediate product for the production of medicinal products.
In the process according to the method, the metal-to-metal compounds used are, for example, magnesium, cadmium or zinc.
Example: 1st part by weight of d 4-17a-methyl-3-oxo-etio- cholenic acid chloride, dissolved. in 30 parts by volume of Xther, a solution of dimethylcadmium (prepared in the usual way from 7.6 parts by weight of magnesium shavings, 30 parts by volume of ether, 10 parts by weight of methyl bromide and 9 parts by weight of cadmium chloride) in ether is added dropwise.
The reaction mixture is then heated to boiling for two hours while stirring, then carefully decomposed with water and finally extracted with ether. The usual processing of the essential extract provides 0.9 parts by weight of raw 17a-methyl-progesterone of the formula
EMI0001.0037
which, after crystallizing from ether, melts petroleum ether at 129 to 130; [a] D-I-113 (in chloroform).
The d 4-17a-methyl-3-oxo-etio-cholenic acid chloride used as the starting material can be prepared from the known d 5-17a-methyl-3-ss-oxy-etio-ehlolenic acid in the following way:
The oxy acid is treated in glacial acetic acid solution with the addition of sodium acetate with 1 mol of bromine, the crude 5,6-di bromide obtained is oxidized with chrointrioxy d in glacial acetic acid solution, and finally, without isolation of intermediate stages, debromination with zinc dust in glacial acetic acid performed.
From 1 part by weight of J5-17a-methyl-3ss-oxy-etio-eholenic acid, after crystallizing the crude product from acetone, 0.8 parts by weight of 4-17a-methyl-3-oxo-etio-cholenic acid are obtained, which melts at 291 to 293:
[a] D = -I-89 (in dioxane). To prepare the acid chloride, the d 4-17a-methyl-3-oxo-etio-eholensä-LLive is taken up in ethanol with a.
Equi valent 0.1N sodium hydroxide solution is added, the solution is evaporated to dryness and the sodium salt obtained is finally dried in a high vacuum at 120 °. The sodium salt is then suspended in absolute benzene and, after adding a little pyridine, oxalyl chloride is added. The reaction is over after 30 minutes, after which the solution is evaporated to dryness.
The crude acid chloride is taken up in ether, the solution of the precipitated sodium chloride is filtered off and reacted directly with dimethylcadmium in the manner described above.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH296566T | 1949-01-31 | ||
| CH284942T | 1949-01-31 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH296566A true CH296566A (en) | 1954-02-15 |
Family
ID=25732465
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH296566D CH296566A (en) | 1949-01-31 | 1949-01-31 | Process for the preparation of a 17-methylpregnene compound. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH296566A (en) |
-
1949
- 1949-01-31 CH CH296566D patent/CH296566A/en unknown
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