DE1912236A1 - Cyclobutanes esp. steroid spirocyclo butanones - Google Patents

Cyclobutanes esp. steroid spirocyclo butanones

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Publication number
DE1912236A1
DE1912236A1 DE19691912236 DE1912236A DE1912236A1 DE 1912236 A1 DE1912236 A1 DE 1912236A1 DE 19691912236 DE19691912236 DE 19691912236 DE 1912236 A DE1912236 A DE 1912236A DE 1912236 A1 DE1912236 A1 DE 1912236A1
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Prior art keywords
methyl
hydrogen
starting material
radical
general formula
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DE19691912236
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German (de)
Inventor
Wiechert Dr Rudolf
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Bayer Pharma AG
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Schering AG
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Priority to DE19691912236 priority Critical patent/DE1912236A1/en
Priority to FI700424A priority patent/FI47094C/en
Priority to DK84270AA priority patent/DK127474B/en
Priority to US15884A priority patent/US3657288A/en
Priority to BR217198/70A priority patent/BR7017198D0/en
Priority to FR707007736A priority patent/FR2034691B1/fr
Priority to CH322470A priority patent/CH555796A/en
Priority to AT206870A priority patent/AT303276B/en
Priority to ES377185A priority patent/ES377185A1/en
Priority to SE02940/70A priority patent/SE361170B/xx
Priority to AU12188/70A priority patent/AU1218870A/en
Priority to BE746966D priority patent/BE746966A/en
Priority to NL7003270A priority patent/NL7003270A/xx
Priority to JP45019233A priority patent/JPS4930828B1/ja
Priority to GB1086070A priority patent/GB1308182A/en
Publication of DE1912236A1 publication Critical patent/DE1912236A1/en
Pending legal-status Critical Current

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    • 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
    • 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
    • A61K31/568—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 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C33/00—Moulds or cores; Details thereof or accessories therefor
    • B29C33/20—Opening, closing or clamping
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29D—PRODUCING PARTICULAR ARTICLES FROM PLASTICS OR FROM SUBSTANCES IN A PLASTIC STATE
    • B29D35/00—Producing footwear
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Mechanical Engineering (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Steroid Compounds (AREA)

Abstract

Steroid spirocyclobutanones of formula (I): (in which C5 C6 is a single or double bond; V is H or CH3; one of T and U is =O, the other is 2H. A represents the structures (II), (III), (IV) or (V). (where W is H, an alkyl residue of tetrahydro-pyranyl or acyl; Z is H or methyl residue; and R is H, acyl or alkyl, pref. lower alkyl). Cpds. have pharmacological (e.g. testicular- and prostatic- inhibitory, ovulation inhibitory) activity and are intermediates for spironolactones.

Description

Cyclobutanone Die Erfindung betrifft ein neues Verfahren zur Herstellung von Cyclobutanonen der allgemeinen Formel I worin R1 und R2 entweder einzeln Alkyl- oder Cycloalkylreste oder gemeinsam unter Einschluß des benachbarten Kohlenstoffatoms 1' des Cyclobutanonringes einen Cycloalkyl- oder einen Steroidrest bedeuten.Cyclobutanones The invention relates to a new process for the preparation of cyclobutanones of the general formula I. where R1 and R2 are either individually alkyl or cycloalkyl radicals or together, including the adjacent carbon atom 1 'of the cyclobutanone ring, denote a cycloalkyl or a steroid radical.

Es wurde gefunden, daß man Cyclobutanone der allgemeinen Formel I erhält, wenn man auf tertiare a-Chlor- oder a-Bromketone der allgemeinen Formel II worin R1 und R2 die oben angegebene Bedeutung haben und X Chlor oder Brom bedeutet, Dimethyimethylensulfoniumoxid einwirken läßt.It has been found that cyclobutanones of the general formula I are obtained if one uses tertiary α-chloro or α-bromo ketones of the general formula II where R1 and R2 have the meanings given above and X is chlorine or bromine, dimethyimethylene sulfonium oxide is allowed to act.

Es ist überraschend, daß bei der Umsetzung von α-Halogenketonen mit Dimethylmethylensulfoniumoxid Cyclobutanone entstehen, a' bekannt ist, daß Ketone mit Dimethylmethylensulfoniumoxid Oxirane bilden (Journ. Am. Chem. Soc. 84 (1962), Seite b67 - 868). im Hinblick auf die genannte Literaturstelle hätte man auch erwarten können, daß ein aus dem a-Halogenketon durch Halogenwasserstoffabspaltung entstandenes a,ß- ungesättigtes Keton zu einem Cyclopropylketon methyleniert wird. Die Bildung von Cyclooutanonen konnte man jedoch nicht erwarten, da allgemein bekannt isl, da die Tendenz zur Vierringbildung nur sehr gering ist.It is surprising that in the implementation of α-haloketones cyclobutanones are formed with dimethylmethylene sulfonium oxide, a 'it is known that ketones form oxiranes with dimethylmethylene sulfonium oxide (Journ. Am. Chem. Soc. 84 (1962), Page b67 - 868). in view of the cited literature one would have expected can that a formed from the a-haloketone by elimination of hydrogen halide a, ß-unsaturated ketone is methylenated to a cyclopropyl ketone. The education Cyclooutanones could not be expected, however, since it is generally known that the tendency towards four-ring formation is only very slight.

Das neue Verfahren zur Herstellung von Cyclooutanonen verläuft unter erstaunlich milden Bedingungen. So genügt es im allgemeinen, die Reaktionskomponenten in einem inerten Lösungsmittel eine Ze1t lang bei Raumtemperatur oder wenig erhöhter Temperatur stehen 2*i lassen. Zur Isolierung und Reinigung der Cyclobutanone werden ,ie üblichen Methoden wie Destillation, Chromatographie und Kristallisation angewandt.The new process for the production of cyclooutanones goes under amazingly mild conditions. So it is generally sufficient to add the reaction components in an inert solvent for one time at room temperature or slightly higher Let the temperature stand 2 * i. Used to isolate and purify the cyclobutanones , ie usual methods such as distillation, chromatography and crystallization are used.

Das als Reagens eingesetzte Dimethylmethylensulfoniumoxid kann aus einem Trimethylsulfoxoniumsalz,wie zum Beispiel dem Halogenid.The dimethylmethylene sulfonium oxide used as a reagent can be selected from a trimethylsulfoxonium salt such as the halide.

Perchlorat oder Methylsulfat, in einem aprotonischen Lösungsmittel wie Dimethylsulfoxid oder Dimethylformamid mit einer wasserfreien Base bei Raumtemperatur freigesetzt werden. Zur Durchführung es erfindungsgemäßen Verfahrene ist es zweckmäßig, das Dimethylmethylensulfoniumoxid nicht zu isolieren, sondern die Reaktionslösung mit dem a-Halogenketon weiter reagieren zu lassen.Perchlorate or methyl sulfate, in an aprotic solvent such as dimethyl sulfoxide or dimethylformamide with an anhydrous base at room temperature be released. To carry it out method according to the invention it is advisable not to isolate the dimethylmethylene sulfonium oxide, but rather to allow the reaction solution to react further with the α-haloketone.

Als inerte Lösungsmittel kommen bei der erfindungsgemäßen Umsetzung demnach vorzugsweise Dimethylsulfoxid und Dimethylformamid infrage.The inert solvents used in the reaction according to the invention therefore preferably dimethyl sulfoxide and dimethylformamide.

ie neue Reaktion ist bei tertiären a-Chlor- oder a-Bromketoner der allgemeinen Formel II durchführbar. Da solche tertiären Halogenketone leicht zugänglich sind, werden mit Hilfe des neuen Verfahrens auch die Cyclobutanone leicht zugänglich. Einige Vertreter, insbesondere die Steroid-Spirocyclobutanone, sind nach dem neuen Verfahren erstmalig erhalten worden.he new reaction is the tertiary a-chloro or a-bromo ketone general formula II feasible. Since such tertiary halogen ketones are easily accessible the cyclobutanones are also easily accessible with the help of the new process. Some representatives, especially the steroid spirocyclobutanone, are after the new one Procedure received for the first time.

Als Ausgangsstoffe der Steroidreihe werden vorzugsweise 17-He ogen-20-ketopregnane benutzt. Das Pregnangerüst kann zum Beispiel du ch Alkyl- und freie oder funktionell abgewandelte Hydroxygruppe suostituiert sein. Auch Ketogruppen können enthalten sein. Reakt- nsfähige Ketogruppen wie gesättigte 3-Ketone oder ungesättigte #'-3-Ketone müssen vor der Umsetzung beispielsweise durch Ketalisierung geschützt werden, wenn man Nebenreaktionen vermeiden will.The starting materials of the steroid series are preferably 17-He ogen-20-ketopregnane used. The pregnancy structure can, for example, be alkyl and free or functional modified hydroxy group be substituted. Can also contain keto groups be. Reactive keto groups such as saturated 3-ketones or unsaturated # '- 3-ketones must be protected from implementation, for example by ketalization, if you want to avoid side reactions.

Cyclobutanone sind wertvolle Zwischenprodukte für organische Synthesen verschiedenster Art. Sie können auch als Zwischenprodukte zur Herstellung wertvoller Arzneimittel dienen.Cyclobutanones are valuable intermediates for organic syntheses of various kinds. They can also be used as intermediate products to produce more valuable Medicinal serve.

Die Erfindung betrifft somit insbesondere auch Steroid-Spirocyclobutanone der allgemeinen Formel I a worin C5#C6 eine Einfach- oder Doppelbindung und V Wass stoff oder eine Methylgruppe bedeuten und worin der Ring A ein der folgenden Strukturen hat: W = Wasserstoff, Alkyl-, Tetrahydropyranyl oder Acylrest, Z = Wasserstoff oder Methylrest und wobei R einen vorzugsweise niederen Alkyl- oder Acylrest darstellt, Z = Wasserstoff oder Methylrest0 Beispiel 1 21,05 g Trimethylsulfoxoniumjodid werden in 363 ml Dimethylsulfoxid mit 3,83 g Natriumhydroxid versetzt und 25 Rinuten in einer Stickstoffatmosphäre bei Raumtemperatur gerührte Es werden dann 14955 g 17-Chlor-3ß-hydroxy-16α-methyl-5-pregnen-2o-on zugegeben, und anschließend wird 1,5 Stunden bei 40° C gerührt. Nach Einrühren in schwach essigsaures Eiswasser wird der Niederschlag abfiltriert, neutral gewaschen, in Methylenchlorid aufgenommen und getrocknet. Das nach dem Eindampfen zur Trockne erhaltene 3ß-Hydroxy-16α-methyl-spiro[5-androsrten-17,l'-cyclobutanj-3'-on wird in 60 ml Pyridin mit 30 ml Aceten hydrid bei Raumtemperatur acetyliert. Das Reaktionsgemisch wird dann in Eiswasser gegossen, der Niederschlag abgesaugt, gewascnen und getrocknet. Nach Ohromatographieren an Silicagel und Umkristallisieren aus Isopropyläther werden 8,5 g 3ß-Acetoxy-16α-methyl-spiro[5-andorsten-17,1'-cyclobutan]-3'-on vom Schmelzpunkt 189,5 - 191° C erhalten. [α]D24° = - 127° (Chloroform).The invention thus in particular also relates to steroid spirocyclobutanones of the general formula I a where C5 # C6 is a single or double bond and V is hydrogen or a methyl group and where the ring A has one of the following structures: W = hydrogen, alkyl, tetrahydropyranyl or acyl radical, Z = hydrogen or methyl radical and where R is a preferably lower alkyl or acyl radical, Z = hydrogen or methyl radical Example 1 21.05 g of trimethylsulfoxonium iodide are mixed with 3.83 g of sodium hydroxide in 363 ml of dimethyl sulfoxide and stirred for 25 minutes in a nitrogen atmosphere at room temperature. 14955 g of 17-chloro-3ß-hydroxy-16α-methyl- 5-pregnen-2o-one is added, and the mixture is then stirred at 40 ° C. for 1.5 hours. After stirring into weakly acetic ice water, the precipitate is filtered off, washed neutral, taken up in methylene chloride and dried. The 3ß-hydroxy-16α-methyl-spiro [5-androsrten-17, l'-cyclobutanj-3'-one obtained after evaporation to dryness is acetylated in 60 ml of pyridine with 30 ml of acetene hydride at room temperature. The reaction mixture is then poured into ice water, and the precipitate is filtered off with suction, washed and dried. After chromatography on silica gel and recrystallization from isopropyl ether, 8.5 g of 3β-acetoxy-16α-methyl-spiro [5-andorstene-17,1'-cyclobutane] -3'-one with a melting point of 189.5 ° -191 ° C. are obtained. [α] D24 ° = - 127 ° (chloroform).

Beispiel 2 2,2 g 17-Chlor-3ß-hydroxy-16α-methyl-17α-pregn-5-en-20-on werden in 50 ml Dimethylsulfoxid mit Dimethylmethylensulfoniumoxid (hergestellt aus 3,16 g Trimethylsulfoxoniumjodid und 576mg Natriumhydroxid) 1 Stunde bei 40° C gerührt. Die Aufarbeitung sowie Acetylierung wird analog Beispiel 1 durchgeführt. Nach Chromatographieren an Silicagel und Umkristallisieren aus Isopropyläther werden 950 mg 3ß-Acetoxy-16α-methyl-spiro[5-androsten-17,1'-cyclobutan ]-3'-on vom Schmelzpunkt 188,5 - 190,5° C erhalten.Example 2 2.2 g of 17-chloro-3β-hydroxy-16α-methyl-17α-pregn-5-en-20-one are prepared in 50 ml of dimethyl sulfoxide with dimethyl methylene sulfonium oxide ( from 3.16 g of trimethylsulfoxonium iodide and 576 mg of sodium hydroxide) for 1 hour at 40 ° C stirred. Work-up and acetylation are carried out analogously to Example 1. After chromatography on silica gel and recrystallization from isopropyl ether 950 mg of 3β-acetoxy-16α-methyl-spiro [5-androstene-17,1'-cyclobutane ] -3'-one obtained from melting point 188.5-190.5 ° C.

[α]D24° = - 125° (Chloroform).[α] D24 ° = -125 ° (chloroform).

Beispiel 3 3,0 g 17-Brom-3ß-hydroxy-16α-methyl-5-pregnen-20-on werden in 75 ml Dimethylsulfoxid mit Dimethylmethylensulfoniumoxid (hergestellt aus 3,21 g Trimethylsulfoxoniumjodid und 692 mg Natriumhydrid (5o-proz. blsuspension)) 75 Minuten bei 40° C gerührt. Die Aufarbeitung, Acetylierung und Reinigung wird wie in Beispiel 1 beschrieben durchgeführt. Es werden 1,2 g 3ß-Acetoxy-16α-methyl-spiro[5-androsten-17,1'-cyclobutan]-3'-on vom Schmelzpunkt 189 - 190,5° C erhalten.Example 3 3.0 g of 17-bromo-3β-hydroxy-16α-methyl-5-pregnen-20-one are prepared in 75 ml of dimethyl sulfoxide with dimethyl methylene sulfonium oxide ( from 3.21 g trimethylsulfoxonium iodide and 692 mg sodium hydride (5% suspension) Stirred for 75 minutes at 40 ° C. The work-up, acetylation and purification will carried out as described in Example 1. 1.2 g of 3β-acetoxy-16α-methyl-spiro [5-androstene-17,1'-cyclobutane] -3'-one are obtained obtained from melting point 189-190.5 ° C.

Beispiel 4 3,0 g 17-Brom-3ß-acetoxy-5α-pregnan-20-on werden in 75 ml Dimethylsulfoxid mit Dimethylmethylensulfoniumoxid (hergesteli+ aus 2,94 g Trimethylsulfoxoniumjodid und 535 mg Natriumhydroxid) 1 Stunde bei Raumtemperatur gerührt. Die Aufarbeitung und Reinigung wird analog Beispiel 1 durchgeführt Nach Umkristallisieren aus Isopropyläther wird 3ß-Acetoxy-spiro[5α-androstan-17,1'- -cyclobutan]-3'-on vom Schmelzpunkt 200,5 -2020 C erhaltene Beispiel 5 1,0 g 17-Chlor-3ß-acetoxy-5α-pregnan-20-on werden in 25 ml Dimethylsulfoxid wie in Beispiel 1 beschrieben umgesetzt und aufgearbeitet. Nach Chromatographieren an Silicagel und Umkritallisieren aus Isopropyläther wird 3ß-Acetoxy-spiroWSaandrostan-17,1'-cyclobutan]-3'-on vom Schmelzpunkt 200,5 -201.5° C erhalten.Example 4 3.0 g of 17-bromo-3β-acetoxy-5α-pregnan-20-one become in 75 ml of dimethyl sulfoxide with dimethyl methylene sulfonium oxide (manufactured from 2.94 g trimethylsulfoxonium iodide and 535 mg sodium hydroxide) for 1 hour at room temperature touched. The work-up and purification is carried out analogously to Example 1 Recrystallization from isopropyl ether is 3ß-acetoxy-spiro [5α-androstane-17,1'- -cyclobutane] -3'-one with a melting point of 200.5 ° -2020 ° C. Example 5 obtained 1.0 g of 17-chloro-3β-acetoxy-5α-pregnan-20-one are reacted in 25 ml of dimethyl sulfoxide as described in Example 1 and worked up. After chromatography on silica gel and recrystallization from isopropyl ether, becomes 3ß-acetoxy-spiroW saandrostane-17,1'-cyclobutane] -3'-one with a melting point of 200.5 ° -201.5 ° C received.

Beispiel 6 40 g 2-Brom-2-methyl-butan-3-on werden wie in Beispiel 1 beschrieben umgesetzt und aufgearbeitet. Nach Destillation wird 3,3-Dimethyl-cyclobutan-l-on erhalten. (Siedepunkt 121 - 1230 C).Example 6 40 g of 2-bromo-2-methyl-butan-3-one are as in example 1 described implemented and processed. After distillation, 3,3-dimethyl-cyclobutan-1-one is obtained obtain. (Boiling point 121 - 1230 C).

Beispiel 7 lo g l-3romcyclohexyl-methylketon werden wie in Beispiel 1 beschrieben umgesetzt und aufgearbeitet. Es wird Spiro[3,5]-nonan-2-on erhalten.Example 7 lo g of l-3romcyclohexyl methyl ketone are as in example 1 described implemented and processed. Spiro [3,5] -nonan-2-one is obtained.

Claims (15)

P a t e n t a-n s p r ü c h eP a t e n t a-n s p r ü c h e 1. Verfahren zur Herstellung von Cyclobutanonen der allgemeinen Formel 1 worin R1 und 22 entweder einzeln Alkyl- oder Cycloalkylreste oder gemeinsam unter Einschluß des benachbarten Kohlenstoffatoms 1' des Cyclobutanonringes einen Cycloalkyl- oder einen Steroidrest bedeuten, dadurch gekennzeichnet, daß man auf tertiäre a-Chlor- oder α-Bromketone der allgemeinen Formel II worin R1 und R2 die oben angegebene Bedeutung haben und X Chlor oder Brom bedeutet, Dimethylmethylensulfoniumoxid einwirken läßt.1. Process for the preparation of cyclobutanones of the general formula 1 in which R1 and 22 are either individually alkyl or cycloalkyl radicals or together, including the adjacent carbon atom 1 'of the cyclobutanone ring, denote a cycloalkyl or steroid radical, characterized in that tertiary α-chlorine or α-bromo ketones of the general formula II where R1 and R2 are as defined above and X is chlorine or bromine, dimethylmethylene sulfonium oxide is allowed to act. 2. Verfahren zur Herstellung von Steroid-Spirocyclobutanonen der allgemeinen Formel I a worin eine Einfach- oder Doppelbindung und V Wasserstoff oder eine Methylgruppe bedeuten und worin der Ring A eine der folgenden Strukturell hat: W = Wasserstoff, Alkyl-, Tetrahydropyranyl- oder Acylrest. 2. Process for the preparation of steroid spirocyclobutanones of the general formula I a wherein is a single or double bond and V is hydrogen or a methyl group and in which the ring A has one of the following structure: W = hydrogen, alkyl, tetrahydropyranyl or acyl radical. Z = Wasserstoff oder Methylrest und wobei R einen vorzugsweise niederen Alkyl- oder Acylrest darstellt, Z r Wasserstoff oder Methylrest dadurch gekennzeichnet, daß man auf 17-Chlor- oder 17-Brom-20-ketopregnane der allgemeinen Formel II a worin V und der Ring A die oben angegebene Bedeutung haben und X Chlor oder Brom bedeutet, limethylmethylensulfoniumoxid einwirken läßt.Z = hydrogen or methyl radical and where R is a preferably lower alkyl or acyl radical, Z r is hydrogen or methyl radical, characterized in that 17-chloro- or 17-bromo-20-ketopregnane of the general formula II a wherein V and the ring A have the meaning given above and X is chlorine or bromine, allows limethylmethylene sulfonium oxide to act. 3. Verfahren nach Anspruch 1 und 2, dadurch gekennzeichnet, daß man 17-Chlor-3ß-hydroxy-16α-methyl-5-pregnen-20-on als Ausgangsmaterial verwendet.3. The method according to claim 1 and 2, characterized in that one 17-chloro-3ß-hydroxy-16α-methyl-5-pregnen-20-one used as starting material. Q. Verfahren nach Anspruch 1 und 2, dadurch gekennzeichnet, daß man 17-Chlor- 3ß-hydroxy-l6a-methyl-17a-pregn-5-en-2o-on als Ausgangsmaterial verwendet.Q. The method according to claim 1 and 2, characterized in that one 17-chloro-3ß-hydroxy-16a-methyl-17a-pregn-5-en-2o-one was used as the starting material. 5. Verfahren nach Anspruch 1 und 2, dadurch gekennzeichnet, daß man 17-Brom-3ß-hydroxy-16α-methyl-5-pregnen-20-on als Ausgangsmaterial verwendet.5. The method according to claim 1 and 2, characterized in that one 17-Bromo-3ß-hydroxy-16α-methyl-5-pregnen-20-one used as starting material. 6. Verfahren nach Anspruch 1 und 2, dadurch gekennzeichnet, daß man 17-Brom-3ß-acetoxy-5α-pregnen-20-on als Ausgangsmaterial verwendet.6. The method according to claim 1 and 2, characterized in that one 17-Bromo-3ß-acetoxy-5α-pregnen-20-one used as starting material. 7. Verfahren nach Anspruch 1 und 2, dadurch gekennzeichnet, daß man 17-Chlor-3ß-acetoxy-5α-pregnen-20-on als Ausgangsmaterial verwendet.7. The method according to claim 1 and 2, characterized in that one 17-chloro-3ß-acetoxy-5α-pregnen-20-one used as starting material. 8. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß man 2-Brom-2-methyl-butan-3-on als Ausgangsmaterial verwendet. 8. The method according to claim 1, characterized in that 2-bromo-2-methyl-butan-3-one used as starting material. 9. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß man l-Bromcyclohexyl-methylketon als Ausgangsmaterial verwendet. 9. The method according to claim 1, characterized in that one l-bromocyclohexyl methyl ketone used as starting material. lo. Cyclobutanone der allgemeinen Formel I, hergestellt nach Anspruch 1.lo. Cyclobutanones of the general formula I, prepared according to claim 1. 11. Steroid-Spirocyclobutanone der allgemeinen Formel I a worin eine Einfach- oder Doppelbindung und V Wasserstoff oder eine Methylgruppe bedeuten und worin der Ring A eine der folgenden Strukturen hat: W = Wasserstoff, Alkyl-, Tetrahydropyranyl- oder Acylrest Z = Wasserstoff ender Methylrest und wobei R einen vorzugsweise niederen Alkyl- oder Acylrest darstellt, Z = Wasserstoff oder Methylrest.11. Steroid spirocyclobutanones of the general formula I a wherein is a single or double bond and V is hydrogen or a methyl group and in which the ring A has one of the following structures: W = hydrogen, alkyl, tetrahydropyranyl or acyl radical Z = hydrogen ender methyl radical and where R is a preferably lower alkyl or acyl radical, Z = hydrogen or methyl radical. 12. 3ß-Hydroxy-16α-methyl-spiro[5-androsten-17,1'-cyclobutan]-3'-on.12. 3β-Hydroxy-16α-methyl-spiro [5-androstene-17,1'-cyclobutane] -3'-one. 13. 3ß-Acetoxy-16α-methyl-spiro[5-androsten-17,1'-cyclobutan]-3'-on.13. 3β-Acetoxy-16α-methyl-spiro [5-androstene-17,1'-cyclobutane] -3'-one. 14. 3ß-Hydroxy-spiro [5α-androstan-17,1'-cyclobutan]-3'-on.14. 3β-Hydroxy-spiro [5α-androstane-17,1'-cyclobutane] -3'-one. 15. 3ß-Acetoxy-spiro [5α-androstan-17,1'-cyclobutan]-3'-on.15. 3β-Acetoxy-spiro [5α-androstane-17,1'-cyclobutane] -3'-one.
DE19691912236 1969-03-06 1969-03-06 Cyclobutanes esp. steroid spirocyclo butanones Pending DE1912236A1 (en)

Priority Applications (15)

Application Number Priority Date Filing Date Title
DE19691912236 DE1912236A1 (en) 1969-03-06 1969-03-06 Cyclobutanes esp. steroid spirocyclo butanones
FI700424A FI47094C (en) 1969-03-06 1970-02-17 Process for the preparation of steroid spirocyclobutanones.
DK84270AA DK127474B (en) 1969-03-06 1970-02-20 Process for the preparation of steroid-spirocyclobutanones.
US15884A US3657288A (en) 1969-03-06 1970-03-02 Cyclobutanones and process for the preparation thereof
BR217198/70A BR7017198D0 (en) 1969-03-06 1970-03-04 CYCLEBUTANONE PRODUCTION PROCESS
FR707007736A FR2034691B1 (en) 1969-03-06 1970-03-04
CH322470A CH555796A (en) 1969-03-06 1970-03-05 PROCESS FOR THE PRODUCTION OF (ALPHA) -, OR (BETA) SUBSTITUTED CYCLOBUTANONS.
AT206870A AT303276B (en) 1969-03-06 1970-03-05 Process for the preparation of cyclobutanones
ES377185A ES377185A1 (en) 1969-03-06 1970-03-05 Cyclobutanones and process for the preparation thereof
SE02940/70A SE361170B (en) 1969-03-06 1970-03-05
AU12188/70A AU1218870A (en) 1969-03-06 1970-03-05 Process forthe manufacture of cyclobutanones
BE746966D BE746966A (en) 1969-03-06 1970-03-06 CYCLOBUTANONES AND THEIR PREPARATION PROCESS
NL7003270A NL7003270A (en) 1969-03-06 1970-03-06
JP45019233A JPS4930828B1 (en) 1969-03-06 1970-03-06
GB1086070A GB1308182A (en) 1969-03-06 1970-03-06 Process for the manufacture of cyclobutanones

Applications Claiming Priority (1)

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DE19691912236 DE1912236A1 (en) 1969-03-06 1969-03-06 Cyclobutanes esp. steroid spirocyclo butanones

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DE1912236A1 true DE1912236A1 (en) 1970-09-17

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