CH491899A - Verfahren zur Herstellung von 4-oder- 4,6-1,2a-Methylen-19-nor-steroiden - Google Patents

Verfahren zur Herstellung von 4-oder- 4,6-1,2a-Methylen-19-nor-steroiden

Info

Publication number: CH491899A
Authority: CH; Switzerland
Prior art keywords: sep; methylene; acetate; steroids; dione
Prior art date: 1966-12-15

Application number

CH1431867A

Other languages

German (de)

English (en)

Inventor

Rudolf Dr Wiechert

Original Assignee

Schering Ag

Priority date (The priority date 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 date listed.)

1966-12-15

Filing date

1967-10-12

Publication date

1970-06-15

1967-10-12 Application filed by Schering Ag filed Critical Schering Ag

1970-06-15 Publication of CH491899A publication Critical patent/CH491899A/de

Links

238000000034 method Methods 0.000 title claims description 10
238000002360 preparation method Methods 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims description 5
239000001257 hydrogen Substances 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
229910052794 bromium Chemical group 0.000 claims description 2
239000003054 catalyst Substances 0.000 claims description 2
239000000460 chlorine Substances 0.000 claims description 2
229910052801 chlorine Inorganic materials 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
210000002837 heart atrium Anatomy 0.000 claims 1
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
239000000463 material Substances 0.000 claims 1
229910000510 noble metal Inorganic materials 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 40
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
229910052938 sodium sulfate Inorganic materials 0.000 description 16
235000011152 sodium sulphate Nutrition 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
239000005457 ice water Substances 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
238000001035 drying Methods 0.000 description 8
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
230000008018 melting Effects 0.000 description 7
238000002844 melting Methods 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
238000010992 reflux Methods 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
239000007795 chemical reaction product Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
238000001556 precipitation Methods 0.000 description 4
230000035484 reaction time Effects 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 3
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 3
229910000039 hydrogen halide Inorganic materials 0.000 description 3
239000012433 hydrogen halide Substances 0.000 description 3
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
239000011734 sodium Substances 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 3
QZLYKIGBANMMBK-UGCZWRCOSA-N 5α-Androstane Chemical compound C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CCC[C@@]2(C)CC1 QZLYKIGBANMMBK-UGCZWRCOSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
239000002585 base Substances 0.000 description 2
238000009835 boiling Methods 0.000 description 2
229910000019 calcium carbonate Inorganic materials 0.000 description 2
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 2
GRWVQDDAKZFPFI-UHFFFAOYSA-H chromium(III) sulfate Chemical compound [Cr+3].[Cr+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRWVQDDAKZFPFI-UHFFFAOYSA-H 0.000 description 2
LXMQZGGLHVSEBA-UHFFFAOYSA-N chromium;trihydrate Chemical compound O.O.O.[Cr] LXMQZGGLHVSEBA-UHFFFAOYSA-N 0.000 description 2
-1 collidine Chemical class 0.000 description 2
239000012043 crude product Substances 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
238000000605 extraction Methods 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
238000002955 isolation Methods 0.000 description 2
239000000155 melt Substances 0.000 description 2
239000011707 mineral Substances 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
150000003128 pregnanes Chemical class 0.000 description 2
239000000047 product Substances 0.000 description 2
238000006798 ring closing metathesis reaction Methods 0.000 description 2
238000006049 ring expansion reaction Methods 0.000 description 2
JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
CPUKWYXYHPOQJH-RDQPJNLGSA-N (8r,9s,10s,13s,14s)-17-ethenyl-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15-dodecahydro-1h-cyclopenta[a]phenanthrene Chemical compound C1CCC[C@]2(C)[C@H]3CC[C@](C)(C(=CC4)C=C)[C@@H]4[C@@H]3CCC21 CPUKWYXYHPOQJH-RDQPJNLGSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical compound ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
230000001195 anabolic effect Effects 0.000 description 1
230000001548 androgenic effect Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000004140 cleaning Methods 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
230000000694 effects Effects 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical class C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000007789 gas Substances 0.000 description 1
230000003152 gestagenic effect Effects 0.000 description 1
239000011521 glass Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
230000016087 ovulation Effects 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
238000000746 purification Methods 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
229910052711 selenium Inorganic materials 0.000 description 1
239000011669 selenium Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000010025 steaming Methods 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
238000003756 stirring Methods 0.000 description 1
RPBNQQGUJBCUGO-UHFFFAOYSA-N sulfanylidenechromium Chemical compound [S].[Cr] RPBNQQGUJBCUGO-UHFFFAOYSA-N 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1

Classifications

- 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
- 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)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CH1431867A 1966-12-15 1967-10-12 Verfahren zur Herstellung von 4-oder- 4,6-1,2a-Methylen-19-nor-steroiden CH491899A (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DESC039970		1966-12-15

Publications (1)

Publication Number	Publication Date
CH491899A true CH491899A (de)	1970-06-15

Family

ID=7435445

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH1431867A CH491899A (de)	1966-12-15	1967-10-12	Verfahren zur Herstellung von 4-oder- 4,6-1,2a-Methylen-19-nor-steroiden

Country Status (4)

Country	Link
CH (1)	CH491899A (da)
DK (1)	DK117295B (da)
NL (1)	NL6717082A (da)
SE (1)	SE337216B (da)

1967
- 1967-10-09 DK DK501967AA patent/DK117295B/da unknown
- 1967-10-12 CH CH1431867A patent/CH491899A/de not_active IP Right Cessation
- 1967-12-11 SE SE16994/67A patent/SE337216B/xx unknown
- 1967-12-14 NL NL6717082A patent/NL6717082A/xx unknown

Also Published As

Publication number	Publication date
SE337216B (da)	1971-08-02
NL6717082A (da)	1968-06-17
DK117295B (da)	1970-04-13

Legal Events

Date	Code	Title	Description
1979-07-13	PL	Patent ceased

Publication	Publication Date	Title
US3210388A (en)	1965-10-05	13alpha-fluoro-17beta-methyl-18-nor steroids
CH491899A (de)	1970-06-15	Verfahren zur Herstellung von 4-oder- 4,6-1,2a-Methylen-19-nor-steroiden
DE2407967A1 (de)	1974-08-29	16-substituierte corticoide und verfahren zu deren herstellung
DE1593524C3 (da)	1974-11-28
DE3715869C2 (da)	1989-05-03
DE1938283A1 (de)	1970-02-05	6-subst.-13-Polycarbonalkyl-18,19-dinorpregn-4-en-3-one,ihre delta?-Dehydro-Analogen,Zwischenprodukte,Verfahren zur Herstellung dieser Verbindungen und ihre Verwendung
DE1518627C3 (de)	1974-04-18	Verfahren zur Dehydrierung von A-Nor-B-homosteroiden
DE1122944B (de)	1962-02-01	Verfahren zur Herstellung von 1ª‡-Methyl-3-ketosteroiden
CH494213A (de)	1970-07-31	Verfahren zur Herstellung von Gonadienonen
DE1643028C3 (de)	1975-01-09	Neue 1,2 alpha -Methylensteroide, Verfahren zu ihrer Herstellung, sowie diese enthaltende Mittel
DE1813083A1 (de)	1969-10-02	17alpha-Acyloxy-11ss-methyl-19-norpregn-4-en-3,20-dione und deren Derivate sowie Verfahren zur Herstellung dieser Verbindungen
AT274260B (de)	1969-09-10	Verfahren zur Herstellung von neuen 21-Fluor-Δ<4,6>-pregnadienen
DE1158507B (de)	1963-12-05	Verfahren zur Herstellung von 6a-Methyl-16-methylen-steroiden
DE944853C (de)	1956-06-28	Verfahren zur Herstellung von in 17 (20)-Stellung ungesaettigten Steroid-21-carbonsaeuren bzw. von deren Salzen und Estern
AT242873B (de)	1965-10-11	Verfahren zur Herstellung von Testosteron-17-chloral-halbacetalestern
DE1668679A1 (de)	1971-08-19	Neue Steroide und deren Herstellung
CH553759A (de)	1974-09-13	Verfahren zur herstellung von neuen 4-chlor-1,2(alpha)-methylen-(delta)4,6-pregnadien-17(alpha)-ol-3,20-dion oder dessen 17estern.
CH513842A (de)	1971-11-30	Verfahren zur Herstellung neuer 3-Hydroxysteroide
CH374654A (de)	1964-01-31	Verfahren zur Herstellung von Steroidalkyläthern
DE1543468A1 (de)	1969-09-18	Verfahren zur Herstellung neuer Cyclopentanophenanthrenderivate
CH524590A (de)	1972-06-30	Verfahren zur Herstellung von 21-Fluor- 4,6-pregnadienen
DE1593430A1 (de)	1970-07-30	Verfahren zur Herstellung von 6,6-AEthylen-9-fluorsteroiden
DE1966921A1 (de)	1975-04-24	17alpha-propadienylsubstituierte 3-ketosteroide und verfahren zu deren herstellung
DE1468638A1 (de)	1969-10-09	Neue Cyclopentanophenanthren-Derivate und Verfahren zu deren Herstellung
DE1468632B1 (de)	1970-08-27	6alpha-Acetylthio-4-en-3-on-steroide und Verfahren zu deren Herstellung