DE1813998C3 - Process for the preparation of 3-methoxy-18-methyl-1,3,5 (10), 6,8-oestrapentaen-17-one - Google Patents
Process for the preparation of 3-methoxy-18-methyl-1,3,5 (10), 6,8-oestrapentaen-17-oneInfo
- Publication number
- DE1813998C3 DE1813998C3 DE1813998A DE1813998A DE1813998C3 DE 1813998 C3 DE1813998 C3 DE 1813998C3 DE 1813998 A DE1813998 A DE 1813998A DE 1813998 A DE1813998 A DE 1813998A DE 1813998 C3 DE1813998 C3 DE 1813998C3
- Authority
- DE
- Germany
- Prior art keywords
- methyl
- oestrapentaen
- methoxy
- bromine
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- 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
- C07J1/0051—Estrane derivatives
- C07J1/0059—Estrane derivatives substituted in position 17 by a keto group
-
- 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
- C07J1/0051—Estrane derivatives
- C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
- C07J1/007—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
-
- 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
- C07J1/0051—Estrane derivatives
- C07J1/0081—Substituted in position 17 alfa and 17 beta
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Steroid Compounds (AREA)
Description
In der Patentanmeldung P 1643 032.3 wird ein Verfahren zur Herstellung von 3-Methoxy-l,3,5(10), 6,8-östrapentaen-17-on (Equdleninmethyläther) vorgeschlagen, dadurch gekennzeichnet, daß man das entsprechende 6,7-Dihydrosteroid mit Brom umsetzt und anschließend aus dem primär gebildeten Bromprodukt Bromwasserstoff abspaltet.In the patent application P 1643 032.3 a process for the production of 3-methoxy-1,3,5 (10), 6,8-oestrapentaen-17-one (equdlenin methyl ether) suggested, characterized in that the corresponding 6,7-dihydrosteroid is reacted with bromine and then splitting off hydrogen bromide from the primarily formed bromine product.
In Weiterentwicklung dieses Verfahrens wurde nun gefunden, daß das im Hauptpatent vorgeschlagene Verfahren nicht allein auf Equileninmethyläther als Ausgangsprodukt beschränkt ist, sondern in gleicher Weise mit 18-Methyl-8(9)-dehydroöstronmethyläther als Ausgangsprodukt durchführbar ist.In a further development of this process it has now been found that the one proposed in the main patent Process is not limited to equilenin methyl ether as the starting product, but in the same way Way with 18-methyl-8 (9) -dehydroöstronmethyläther is feasible as a starting product.
Die vorliegende Erfindung betrifft somit eine Weiterentwicklung des Verfahrens gemäß Patentanmeldung P 1643 032.3 zur Herstellung von 3-Methoxy-18-methyl-l,3,5(10) o.e-östrapentaen-lT-on, dadurch gekennzeichnet, daß man als Ausgangssteroid 18-MethyI-8(9)-dehydroöstronmethyIäther verwendet und diesen gemäß Hauptpatent mit Brom umsetzt und anschließend aus dem primär gebildeten Bromprodukt Bromwasserstoff abspaltet.The present invention thus relates to a further development of the method according to the patent application P 1643 032.3 for the preparation of 3-methoxy-18-methyl-1,3,5 (10) o.e-oestrapentaen-IT-one, thereby characterized in that 18-methyl-8 (9) -dehydroöstronmethyIäther is used as the starting steroid and this reacts according to the main patent with bromine and then from the primarily formed bromine product Splits off hydrogen bromide.
Das Verfahrensprodukt (18-Methyl-3-Methoxyl,3,5(10),6,8-östrapentaen-17-on) ist neu. Es ist ein wichtiges Ausgangssteroid zur Herstellung pharmazeutisch wirksamer Steroidsubstanzen.The process product (18-methyl-3-methoxyl, 3,5 (10), 6,8-oestrapentaen-17-one) is new. It is an important starting steroid for manufacture pharmaceutically effective steroid substances.
Wie bereits im Rahmen der Hauptanmeldung ausgeführt, war die Durchführbarkeit des erfindungsgemäßen Verfahrens insofern höchst überraschend, als nicht bekannt ist, daß bei der Umsetzung von östronmethyläther mit Brom eine Dehydrierung im B-Ring erfolgt; S lau η white (J. org. ehem. 27 [1962], 1749) konnte unter ähnlichen Bedingungen lediglich eine Bromierung von östron bzw. östradiol im A-Ring erreichen.As already stated in the context of the main application, the feasibility of the invention was Method highly surprising in that it is not known that in the implementation of estrone methyl ether with bromine a dehydrogenation takes place in the B-ring; S lau η white (J. org. Formerly 27 [1962], 1749), under similar conditions, only a bromination of oestrone or oestradiol in the A ring was possible reach.
Das erfindungsgemäße Verfahren wird — wie ebenfalls im Rahmen der Hauptanmeldung ausgeführt — bei vorzugsweise niederer Reaktionstemperatur, z. B. zwischen etwa 0° C und Raumtemperatur, in bei Bromierungsreaktionen üblicherweise angewandten Lösungsmitteln, vorzugsweise in Schwefelkohlenstoff oder Tetrachlorkohlenstoff, durchgeführt. Die Halogenwasserstoffabspaltung erfolgt bereits ohne besonderen Zusatz von hierbei üblichen Reagenzien. The method according to the invention is - as also carried out in the context of the main application - at a preferably lower reaction temperature, z. B. between about 0 ° C and room temperature, in commonly used in bromination reactions Solvents, preferably in carbon disulfide or carbon tetrachloride carried out. The splitting off of hydrogen halide takes place without any special addition of the usual reagents.
25 g 18-Methyl-8(9)-dehydroöstronmethyläther werden in 2,5 1 Tetrachlorkohlenstoff oder Schwefelkohlenstoff gelöst und bei einer Temperatur von 0 bis 5° C innerhalb von 30 Minuten mit einer Lösung von 5,45 ml Brom (1,08 Äquivalente) in 750 ml Tetrachlorkohlenstoff oder Schwefelkohlenstoff versetzt. Fünf Stunden wird bei einer Temperatur von 0 bis 5° C nachgerührt. Anschließend wird die bromfreie Lösung mit Wasser neutral gewaschen, mit Natriumsulfat getrocknet und im Vakuum zur Trockne eingeengt. Der Rückstand wird mit 50 ml Isopropyläther aufgenommen und auf 0° C abgekühlt. Nach 16 Stunden erhält man 10,7 g 18-Methylequileninmethyläther; 25 g of 18-methyl-8 (9) -dehydroestrone methyl ether are dissolved in 2.5 l of carbon tetrachloride or carbon disulfide dissolved and at a temperature of 0 to 5 ° C within 30 minutes with a solution of 5.45 ml of bromine (1.08 equivalents) in 750 ml of carbon tetrachloride or carbon disulfide. The mixture is stirred at a temperature of 0 to 5 ° C. for five hours. Then the bromine-free Solution washed neutral with water, dried with sodium sulfate and in vacuo to Concentrated to dryness. The residue is taken up in 50 ml of isopropyl ether and cooled to 0 ° C. After 16 hours, 10.7 g of 18-methylequilenin methyl ether are obtained;
F. 175 bis 179° C; [«]„ = +22,9° (CHCl3).Mp 175-179 ° C; [«]" = + 22.9 ° (CHCl 3 ).
Claims (2)
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1813998A DE1813998C3 (en) | 1968-12-06 | 1968-12-06 | Process for the preparation of 3-methoxy-18-methyl-1,3,5 (10), 6,8-oestrapentaen-17-one |
| CH1739469A CH518920A (en) | 1967-07-26 | 1969-11-21 | 3-methoxy-18-methyl-1,3,5 (10),6,8-oestrapent |
| NL6918197A NL6918197A (en) | 1968-12-06 | 1969-12-03 | |
| GB59715/69A GB1291106A (en) | 1968-12-06 | 1969-12-08 | 3-methoxy-18-methyl-1,3,5(10),6,8-oestrapentaen-17-one and process for its manufacture |
| FR6942319A FR2025577A6 (en) | 1968-12-06 | 1969-12-08 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1813998A DE1813998C3 (en) | 1968-12-06 | 1968-12-06 | Process for the preparation of 3-methoxy-18-methyl-1,3,5 (10), 6,8-oestrapentaen-17-one |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE1813998A1 DE1813998A1 (en) | 1970-09-17 |
| DE1813998B2 DE1813998B2 (en) | 1975-04-24 |
| DE1813998C3 true DE1813998C3 (en) | 1975-12-11 |
Family
ID=5715914
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE1813998A Expired DE1813998C3 (en) | 1967-07-26 | 1968-12-06 | Process for the preparation of 3-methoxy-18-methyl-1,3,5 (10), 6,8-oestrapentaen-17-one |
Country Status (4)
| Country | Link |
|---|---|
| DE (1) | DE1813998C3 (en) |
| FR (1) | FR2025577A6 (en) |
| GB (1) | GB1291106A (en) |
| NL (1) | NL6918197A (en) |
-
1968
- 1968-12-06 DE DE1813998A patent/DE1813998C3/en not_active Expired
-
1969
- 1969-12-03 NL NL6918197A patent/NL6918197A/xx not_active Application Discontinuation
- 1969-12-08 GB GB59715/69A patent/GB1291106A/en not_active Expired
- 1969-12-08 FR FR6942319A patent/FR2025577A6/fr not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| FR2025577A6 (en) | 1970-09-11 |
| DE1813998A1 (en) | 1970-09-17 |
| DE1813998B2 (en) | 1975-04-24 |
| NL6918197A (en) | 1970-06-09 |
| GB1291106A (en) | 1972-09-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE1813998C3 (en) | Process for the preparation of 3-methoxy-18-methyl-1,3,5 (10), 6,8-oestrapentaen-17-one | |
| DE1200813B (en) | Process for the production of 6-fluorosteroids of the androstane or pregnane series or of corresponding 19-nor compounds | |
| CH518920A (en) | 3-methoxy-18-methyl-1,3,5 (10),6,8-oestrapent | |
| CH518272A (en) | Process for the manufacture of 4-halogeno-1 2alpha 6 | |
| DE1122944B (en) | Process for the preparation of 1ª ‡ -Methyl-3-ketosteroids | |
| DE1643028C3 (en) | New 1,2 alpha -methylene steroids, processes for their production and agents containing them | |
| AT233177B (en) | Process for the preparation of the new 6α-methyl-17α-hydroxyprogesterone and its esters | |
| DE2016783C3 (en) | Process for converting a 17β-hydroxy steroid into the corresponding 17α-hydroxy compound | |
| DE1593524C3 (en) | ||
| DE1643032A1 (en) | Process for the preparation of 3-methoxy-1,3,5 (10), 6,8-oestrapentaen-17-one | |
| AT224821B (en) | Process for the preparation of Δ1, 4-pregnadiene-17α, 21-diol-3, 20-dione | |
| AT250578B (en) | Process for the preparation of 3-enol ethers | |
| CH531498A (en) | Cmpds. of formulae (I), (II) and (III):- where X = H, Cl or F R' = OH or acyloxy R2 = OH or acyloxy or with R' is alkylidenedioxy R3 = | |
| DE1113453B (en) | Process for the production of substitution products of Reichsteins-Substance-S or their 21-acylates | |
| DE1267219B (en) | Process for the separation of 17alpha-AEthinyl-19-nor-delta 4-androsten-17beta-ol-3-one | |
| DE1643035B2 (en) | 15BETA, 16BETA-METHYLEN-5ALPHA -ANDROST-L-ENE, PROCESS FOR THEIR MANUFACTURING AND THE PRODUCTS CONTAINED | |
| DE1096902B (en) | Process for the preparation of 16, 17-methylene-20-keto-steroids | |
| DE1076127B (en) | Process for the production of anabolic steroids with low androgenic side effects | |
| CH274233A (en) | Process for the preparation of a compound of the cyclopentanopolyhydrophenanthrene series which contains an oxy group in ring C. | |
| DE1145170B (en) | Process for the preparation of 9,11-oxidosteroids of the androstane and pregnane series | |
| CH549001A (en) | Halo-pregnanes anti-inflammatories | |
| DE1156800B (en) | Process for the preparation of 17ª ‰ -acyloxy-3-keto-19-nor-í¸-androstadienes or of OEstradiol-17ª ‰ -monoacylates | |
| CH334146A (en) | Process for the preparation of allopregnan-3,6,11,20-tetron | |
| DE1173895B (en) | Process for the preparation of 17-oxygenated derivatives of 19-nor-4-androsten-3-one substituted in the 4-position | |
| DE1031790B (en) | Process for the preparation of new biologically active 19-norsteroid compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C3 | Grant after two publication steps (3rd publication) | ||
| E77 | Valid patent as to the heymanns-index 1977 | ||
| 8340 | Patent of addition ceased/non-payment of fee of main patent |