DE1187237B - Process for the production of 4-hydroxy-3-keto-delta-steroids of the androstane or de9-nor-androstane series - Google Patents
Process for the production of 4-hydroxy-3-keto-delta-steroids of the androstane or de9-nor-androstane seriesInfo
- Publication number
- DE1187237B DE1187237B DES83661A DES0083661A DE1187237B DE 1187237 B DE1187237 B DE 1187237B DE S83661 A DES83661 A DE S83661A DE S0083661 A DES0083661 A DE S0083661A DE 1187237 B DE1187237 B DE 1187237B
- Authority
- DE
- Germany
- Prior art keywords
- hydroxy
- androstane
- keto
- steroids
- testosterone
- 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.)
- Pending
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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Description
Verfahren zur Herstellung von 4-Hydroxy-3-keto-44steroiden der Androstan- bzw. der 19-Nor-androstan-Reihe Die vorliegende Erfindung bezieht sich auf ein Verfahren zur Herstellung von 4-Hydroxy-3-ketod 4-steroiden der Androstan- bzw. der 19-Nor-androstan-Reihe.Process for the production of 4-hydroxy-3-keto-44steroids of the androstan- or the 19-nor-androstane series. The present invention relates to a method for the production of 4-hydroxy-3-ketod 4-steroids of the androstane and 19-nor-androstane series.
Es wurde gefunden, daß 4-Chlor-3-keto-44-androstene (I) der lOß-Methyl- bzw. 19-Nor-Reihe, mit einem Alkalihydroxyd in einem aliphatischen tertiären Alkohol unter Inertgasatmosphäre behandelt, direkt in einer einzigen Stufe die entsprechenden 4-Hydroxy-3-keto-d 4-androstene ergeben.It has been found that 4-chloro-3-keto-44-androstene (I) is the lOß-methyl or 19-Nor series, with an alkali hydroxide in an aliphatic tertiary alcohol treated under an inert gas atmosphere, the corresponding directly in a single stage 4-Hydroxy-3-keto-d 4-androstene result.
Nach der vorliegenden Erfindung werden 4-Chlor-3-keto-44-steroide der Androstan- bzw. der 19-Norandrostan-Reihe (nach B. C a m e r i n o und Mitarbeiter hergestellt: belgische Patentschriften 549701, 552152, 552 153 und 557 735) in einem aliphatischen tert.-Alkohol, wie in tert.-Butylalkohol oder tert.-Amylalkohol gelöst und mit einem Überschuß an wäßrigem Alkalihydroxyd, wie Natriumhydroxyd oder Kaliumhydroxyd, in inerter Atmosphäre, wie Stickstoff, in der Wärme, vorzugsweise bei der Rückflußtemperatur des verwendeten Alkohols während eines Zeitraumes von wenigen Minuten bis einigen Stunden, umgesetzt. Hierauf wird das Reaktionsgemisch mit organischen Säuren, wie Essigsäure, oder mit anorganischen verdünnten Säuren neutralisiert, dann mit Wasser verdünnt, und das Steroid wird vorzugsweise durch Extrahieren mit einem üblichen, mit Wasser unmischbaren organischen Lösungsmittel in an sich bekannter Weise isoliert.According to the present invention there are 4-chloro-3-keto-44-steroids the androstane or 19-norandrostane series (after B. C a m e r i n o and co-workers manufactured: Belgian patents 549701, 552152, 552 153 and 557 735) in one aliphatic tertiary alcohol, such as dissolved in tertiary butyl alcohol or tertiary amyl alcohol and with an excess of aqueous alkali hydroxide, such as sodium hydroxide or potassium hydroxide, in an inert atmosphere, such as nitrogen, in the warm, preferably at the reflux temperature of the alcohol used over a period of a few minutes to a few Hours, implemented. The reaction mixture is then treated with organic acids, such as Acetic acid, or neutralized with inorganic dilute acids, then with water diluted, and the steroid is preferably extracted by extracting with a conventional, water-immiscible organic solvents isolated in a manner known per se.
Die so erhaltenen rohen Produkte, d. h. 4-Hydroxy-3-keto-44-androstene der lOß-Methyl- bzw. 19-Nor-Reihe, können entweder durch Kristallisieren aus organischen Lösungsmitteln oder durch Chromatographie an adsorbierenden Substanzen, wie Florisil (Handelsmarke), und darauffolgendes Eluieren und Kristallisieren weitergereinigt werden, oder sie können zur Weiterverarbeitung durch Acylierung der anwesenden sek.-Hydroxygruppen mit dem Chlorid oder Anhydrid einer organischen Säure, gegebenenfalls in Anwesenheit tert.-Amine, und darauffolgende Reinigung nach den üblichen Verfahren in ihre Acylderivate übergeführt werden.The raw products thus obtained, i.e. H. 4-hydroxy-3-keto-44-androstene the lOß-Methyl- or 19-Nor series, can either by crystallization from organic Solvents or by chromatography on adsorbing substances, such as Florisil (Trade mark), and subsequent elution and crystallization further purified or they can be used for further processing by acylation of the secondary hydroxyl groups present with the chloride or anhydride of an organic acid, optionally in the presence tert-amines, and subsequent purification according to the usual methods into their acyl derivatives be transferred.
Die 4-Hydroxy-3-keto-44-steroide der Androstan-bzw. der 19-Nor-androstan-Reihe sind in der Therapie als anabole und androgene Stoffe nützlich.The 4-hydroxy-3-keto-44-steroids of the androstane or. the 19-nor-androstane series are useful in therapy as anabolic and androgenic substances.
Die folgenden Beispiele erläutern das erfindungsgemäße Verfahren.The following examples explain the process according to the invention.
Beispiel l 4-Hydroxy-testosteron 0,500g 4-Chlor-testosteron-acetat in 40m1 tert.-Butanol (oder tert.-Amylalkohol) werden 15 Minuten in Stickstoffatmosphäre am Rückfluß erhitzt, worauf eine Lösung von 0,500 g Kaliumhydroxyd (oder Natriumhydroxyd) in 10 ml Wasser hinzugefügt wird. 1 Stunde danach wird die Lösung mit Essigsäure neutralisiert und mit Äthylacetat extrahiert. Der organische Extrakt wird zuerst mit 5°/oiger Natronlauge und schließlich mit Wasser neutral gewaschen und das Lösungsmittel im Vakuum abgedampft.Example 1 4-Hydroxy-testosterone 0.500 g of 4-chloro-testosterone acetate in 40m1 of tert-butanol (or tert-amyl alcohol) are 15 minutes in a nitrogen atmosphere heated to reflux, whereupon a solution of 0.500 g of potassium hydroxide (or sodium hydroxide) in 10 ml of water is added. 1 hour thereafter, the solution is with acetic acid neutralized and extracted with ethyl acetate. The organic extract comes first washed neutral with 5% sodium hydroxide solution and finally with water and the solvent evaporated in vacuo.
Der Rückstand (UV-Absorption: @maX = 280 m#t mit E = 7000) wird an Florisil chromatographiert. Aus den mit Benzol-Äthyläther 1:1 eluierten Fraktionen kristallisiert durch Zusatz von Äthyläther 4-Hydroxy-testosteron ; Fp. 221 bis 223'C. Beispiel 2 4-Hydroxy-17cx-methyl-testosteron In ähnlicher Weise wie im Beispiel 1 erhält man aus 0,500 g 4-Chlor-17x-methyl-testosteron das 4-Hydroxy-17x-methyl-testosteron: Fp. 170 bis 172°C.The residue (UV absorption: @ max = 280 m # t with E = 7000) is on Florisil chromatographed. From the fractions eluted with benzene-ethyl ether 1: 1 crystallized by adding ethyl ether 4-hydroxy-testosterone; M.p. 221 to 223'C. Example 2 4-Hydroxy-17cx-methyl-testosterone In a manner similar to the example 1, 4-hydroxy-17x-methyl-testosterone is obtained from 0.500 g of 4-chloro-17x-methyl-testosterone: Mp 170-172 ° C.
Beispiel 3 4-Hydroxy-19-nor-testosteron In ähnlicher Weise wie im
Beispiel 1 erhält man aus 1,5 g 4-Chlor-19-nor-testosteron-acetat das 4-Hydroxy-19-nor-testosteron:
Fp. 188 bis 190°C.
Claims (1)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT1187237X | 1962-02-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
DE1187237B true DE1187237B (en) | 1965-02-18 |
Family
ID=11432885
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DES83661A Pending DE1187237B (en) | 1962-02-13 | 1963-02-08 | Process for the production of 4-hydroxy-3-keto-delta-steroids of the androstane or de9-nor-androstane series |
Country Status (1)
Country | Link |
---|---|
DE (1) | DE1187237B (en) |
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1963
- 1963-02-08 DE DES83661A patent/DE1187237B/en active Pending
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