DK146097B - Fremgangsmaade til fremstilling af 11-ketosteroider eller 11-keto-d-homosteroider - Google Patents
Fremgangsmaade til fremstilling af 11-ketosteroider eller 11-keto-d-homosteroider Download PDFInfo
- Publication number
- DK146097B DK146097B DK515580AA DK515580A DK146097B DK 146097 B DK146097 B DK 146097B DK 515580A A DK515580A A DK 515580AA DK 515580 A DK515580 A DK 515580A DK 146097 B DK146097 B DK 146097B
- Authority
- DK
- Denmark
- Prior art keywords
- ketosteroids
- keto
- preparing
- homosteroids
- procedure
- Prior art date
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- 238000000034 method Methods 0.000 title description 13
- 239000002904 solvent Substances 0.000 abstract description 8
- 238000009835 boiling Methods 0.000 abstract description 6
- 238000010438 heat treatment Methods 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 150000003431 steroids Chemical class 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- -1 di- Chemical class 0.000 description 2
- TXCDCPKCNAJMEE-UHFFFAOYSA-N dibenzofuran Chemical compound C1=CC=C2C3=CC=CC=C3OC2=C1 TXCDCPKCNAJMEE-UHFFFAOYSA-N 0.000 description 2
- 150000005218 dimethyl ethers Chemical class 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 1
- JQCVPZXMGXKNOD-UHFFFAOYSA-N 1,2-dibenzylbenzene Chemical class C=1C=CC=C(CC=2C=CC=CC=2)C=1CC1=CC=CC=C1 JQCVPZXMGXKNOD-UHFFFAOYSA-N 0.000 description 1
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 1
- GRZXREUFTYRRJH-UHFFFAOYSA-N 10-oxatetracyclo[6.5.0.02,7.09,11]trideca-1,3,5,7,12-pentaene Chemical compound C12=CC=CC=C2C2=C1C1OC1C=C2 GRZXREUFTYRRJH-UHFFFAOYSA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- BWZVCCNYKMEVEX-UHFFFAOYSA-N 2,4,6-Trimethylpyridine Chemical compound CC1=CC(C)=NC(C)=C1 BWZVCCNYKMEVEX-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- RZRPTBIGEANTGU-IRIMSJTPSA-N adrenosterone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 RZRPTBIGEANTGU-IRIMSJTPSA-N 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- TZLFWVPLPHJLSE-UHFFFAOYSA-N cyclopentane phenanthrene Chemical class C1CCCC1.C1=CC=C2C3=CC=CC=C3C=CC2=C1 TZLFWVPLPHJLSE-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000000374 eutectic mixture Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- 238000001149 thermolysis Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
-
- 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
- C07J1/0003—Androstane derivatives
- C07J1/0011—Androstane derivatives substituted in position 17 by a keto group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
- C07J13/005—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17 with double bond in position 16 (17)
-
- 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
- C07J5/0007—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 not substituted in position 17 alfa
- C07J5/0023—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 not substituted in position 17 alfa substituted in position 16
- C07J5/003—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 not substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group including 16-alkylidene substitutes
- C07J5/0038—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 not substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group including 16-alkylidene substitutes by an alkyl group
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Description
1 146097
Opfindelsen angår en fremgangsmåde til fremstilling af 11-ketosteroider eller 11-keto-D-homosteroider ud fra 9a-halo-gen-11β-hydroxysteroider eller 9a-halogen-11Ø-hydroxy-D-homosteroider, hvilken fremgangsmåde er ejendommelig ved det i kravets kendetegnende del angivne.
Med halogen skal forstås chlor eller brom.
Forbindelserne, der kan fremstilles ifølge opfindelsen, er enten selv kendte biologisk virksomme forbindelser eller tjener som mellemprodukter til fremstillingen af sådanne forbindelser.
ll-keto-5a-pregnaner og deres D-homoanaloge kendes således som i.v.-anæstetika.
Cortisonet og andre cortikoider kan således fremstilles ved sidekædeopbygning af 4-androsten-3,ll,17-trionet.
Ifølge de kendte metoder fås 11-ketosteroider af de tilsvarende * 1)-steroider, hvorhos bromhydrinet først dannes med bromundersyrling, 9a-bromatomet derpå fjernes reduktivt med f.eks. tributyltinhydrid, og endelig 11 (5-hydroxyforbindelsen bliver oxideret til 11-ketoforbindel-sen.
De kendte kemiske metoder har dog den ulempe, at de enten forløber over flere trin eller giver utilfredsstillende udbytter.
Forløbet af reaktionen ifølge opfindelsen var for såvidt overraskende, da man ville vente, at der ved opvarmning til temperaturer over de pågældende forbindelsers smeltepunkt ville optræde termiske dekomponeringer og omlejringer. Der måtte også forventes ganske andre reaktioner. Ved opvarmning af ga-chlor-lltf-hydroxy-A1''♦-S-ketosteroider i nærværelse af kaliumacetat eller -carbonat får man f.eks. de tilsvarende 9 β, 11 tf-epoxy- Δ1' ‘♦-S-ketosteroider (Fieser &
Fieser, Steroids, 1961, side 743). Eller der fås Δ9-11-hydroxysteroider ved opvarmning i collidin eller pyridin (DE offentliggørelsesskrift nr. 2.817.081).
146097
Ved fremgangsmåden ifølge opfindelsen fås sterisk homogene forbindelser.
De som udgangsmateriale anvendte 9a-halogen-113-hydroxysteroider kan i sig selv være substitueret yderligere.
Som substituenter kommer f.eks. lavere alkylgrupper såsom methyl i 2-, 6-, 16-, 18- og 21-stillingen og hydroxygruppen 5 i 3-stillingen på tale. Et yderligere halogenatom såsom fluor eller chlor kan findes i 6-stillingen. Også alkynylgrupper såsom ethynylgruppen i 17-stillingen og ketogrupper kan imidlertid også findes i 3- eller 20-stillingen. En methylengruppe kan være i 1,2- og/eller 6,7-stillingen. Dobbeltbindinger kan 10 findes il-, 4-, 5- og/eller 6-stillingen. Acyloxygrupper kan optræde i 3- og/eller 21-stillingen. Fremgangsmåden ifølge opfindelsen er ikke begrænset til steroider af cyklopentan-phenanthrenrækken. Den kan også anvendes på steroider af D-homorækken.
15 Såfremt der i 17a-stillingen er en acyleret hydroxygruppe, kan denne under reaktionsbetingelserne ifølge opfindelsen afspal- 1 6 tes under dannelse af en Δ -dobbeltbinding.
Fremgangsmåden ifølge opfindelsen gennemføres således, at man opløser udgangsmaterialet i det ifølge opfindelsen anvendte 20 opløsningsmiddel og opvarmer ved temperaturer på 180-350°C, fortrinsvis 200-3Q0°C i et tidsrum fra 3 min. til 20 min.
Egnede opløsningsmidler til gennemførelse af fremgangsmåden ifølge opfindelsen er inaktive, højtkogende aprotiske opløsningsmidler såsom f.eks. biphenyl, biphenylenoxid, dibenzyl= 25 benzen, oligoglycoldimethylethere såsom di-, tri- og poly= glycol-200-dimethylenethere samt poly-C^_g-alkandioldimethyl= ethere og deres indbyrdes blandinger. Disse væsker er for tiden i handelen. Under navnet "Dowtherm" ® A fås en eutektisk blanding af biphenyl og dibenzofuran (omtrentlig kogepunkt 50 285°C); under navnet "Marlotherm" ® S dibenzylbenzen-isomer- blandinger (omtrentlig kogepunkt 39Q°C) og under betegnelsen polyglycol-20Q-dimethylether,en homolog blanding af penta= ethylenglycoldimethylether CH^O (C^CI^O) nCHg, n = 2-10 (kogepunkt s interval 240-350°C).
146097 3
Det ifølge opfindelsen anvendte opløsningsmiddel anvendes i en mængde på 2-50, fortrinsvis 5-20 vægtdele beregnet på mængden af udgangsmaterialet.
Reaktionen ifølge opfindelsen kan gennemføres ved atmosfærisk 1 4 5 tryk. Til varmefølsomme stoffer såsom f.eks. ved Δ ' -steroider med et halogenatom i 6-stillingen anbefales det at arbejde ved reduceret tryk. Det i praksis anvendelige tryk ligger ved 1-30 mm Hg.
Det er hensigtsmæssigt at opvarme reaktionsblandingen under 10 en beskyttelsesgasatmosfære såsom f.eks. nitrogen for at udelukke indvirkningen af oxygen. Også tilførslen af fast stof sker fortrinsvis under beskyttelsesgas til det forud til den ønskede temperatur indstillede opløsningsmiddel. Forløbet af termolysen kan let følges tyndtlagskromatografisk. Efter 15 endt reaktion afkøles reaktionsblandingen, og den oparbejdes på sædvanlige måde såsom ved filtrering, vaskning og elu-ering.
En foretrukket oparbejdningsform er fjernelsen af opløsningsmidlet ved vanddampdestillation, tørring af resten og omkry-20 stallisation.
Generelt set har fremgangsmåden ifølge opfindelsen den fordel, at den består af en helt enkel behandling. Stoffer opvarmes i opløsningsmidlet og adskilles efter reaktionen igen fra opløsningsmidlet .
25 En yderligere fordel ved fremgangsmåden består i at afspaltet halogenhalogenid eller let flygtige organiske syrer,såsom eddike- eller propionsyre, undviger fra reaktionsvæsken ved opvarmningen. En neutralisation er ikke nødvendig. Syrekatalyserede oplejringer, såsom f.eks. dienonphenol-omlejringen 1 4 30 af A ' -3-ketosteroider,kan slet ikke først optræde.
De følgende eksempler skal belyse fremgangsmåden ifølge op- 4 146097 findelsen.
Eksempel 1 1 g 9a-chlor-110-hydroxy-16a-methyl-21-trimethylacetoxy-l,4-pregnadien-3,20-dion omrøres i 4 ml "Marlotherm" ® S i 5 min.
5 ved 300°C oliebadtemperatur under argon. Efter· afkøling fortyndes med toluen og kromatograferes på silicagel. Der fås således 650 mg 16a-methyl-21-trimethylacetoxy-l,4-pregnadien- 3,11,20-trion.
Smeltepunkt 201-202,5°C (acetone/hexan).
10 Eksempel 2 3 g 9a-chlor-ll(3-hydroxy-16a-methyl-21-trimethylacetoxy-l,4-pregnadien-3,20-dion omrøres i 10 ml polyglycol-200-dimethyl= ether (kogepunktsinterval 240-350°C) i 8 min. ved 300°C oliebadtemperatur under argon. Efter afkøling hældes i 200 ml is-15 vand, og det udfældede produkt suges fra og tørres. Efter omkrystallisation fra acetone/hexan fås 1,4 g 16a-methyl-21-triiaethylacetoxy-l,4-pregnadien-3,ll,20-trion, som er identisk med den ifølge eksempel 1 fremstillede forbindelse.
Eksempel 3 20 i g 9a-chlor-17a,21-dipropionyloxy-lip-hydroxy-160-methyl- l,4-pregnadien-3,20-dion tilsættes i fast form til 10 ml til 280°C forud opvarmet "Marlotherm"® under omrøring og nitrogengastilførsel. Temperaturen holdes i 4 min. og får derpå lov til at falde. Opløsningen kromatograferes på sili-25 cagel. Med hexan elueres først "Marlotherm" ® og derpå kromatograferes med hexan/eddikeester (0-30%). Der fås 730 mg 168-methyl-21-propionyloxy-l,4,16-pregnatrien-3,11,20-trion (92% af det teoretiske udbytte) med smeltepunkt 173-178°C.
UV; ε243 = 19600
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2950026 | 1979-12-10 | ||
| DE2950026A DE2950026C2 (de) | 1979-12-10 | 1979-12-10 | Verfahren zur Herstellung von 11-Ketosteroiden |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK515580A DK515580A (da) | 1981-06-11 |
| DK146097B true DK146097B (da) | 1983-06-27 |
| DK146097C DK146097C (da) | 1983-12-05 |
Family
ID=6088284
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK515580A DK146097C (da) | 1979-12-10 | 1980-12-03 | Fremgangsmaade til fremstilling af 11-ketosteroider eller 11-keto-d-homosteroider |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US4315866A (da) |
| EP (1) | EP0030368B1 (da) |
| JP (1) | JPS5692900A (da) |
| AT (1) | ATE2534T1 (da) |
| CA (1) | CA1141750A (da) |
| DE (2) | DE2950026C2 (da) |
| DK (1) | DK146097C (da) |
| HU (1) | HU182250B (da) |
| IE (1) | IE50611B1 (da) |
| IL (1) | IL61601A (da) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE35517E (en) * | 1987-08-25 | 1997-05-20 | University Of Southern California | Method, compositions, and compounds for modulating brain excitability |
| US5232917A (en) * | 1987-08-25 | 1993-08-03 | University Of Southern California | Methods, compositions, and compounds for allosteric modulation of the GABA receptor by members of the androstane and pregnane series |
| US5120723A (en) * | 1987-08-25 | 1992-06-09 | University Of Southern California | Method, compositions, and compounds for modulating brain excitability |
| FR2691968B1 (fr) * | 1992-06-04 | 1994-07-29 | Roussel Uclaf | Nouveau procede de preparation d'un derive sterouide 11-ceto. |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL7802905A (nl) * | 1977-04-21 | 1978-10-24 | Hoffmann La Roche | Werkwijze voor het bereiden van d-homosteroiden. |
| DE2929558C2 (de) * | 1979-07-18 | 1982-03-11 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Verfahren zur Herstellung von Δ↑9↑↑(↑↑1↑↑1↑↑)↑ und/oder Δ↑1↑↑6↑ ungesättigten Steroiden |
-
1979
- 1979-12-10 DE DE2950026A patent/DE2950026C2/de not_active Expired
-
1980
- 1980-12-01 IL IL61601A patent/IL61601A/xx unknown
- 1980-12-03 DK DK515580A patent/DK146097C/da not_active IP Right Cessation
- 1980-12-04 EP EP80107595A patent/EP0030368B1/de not_active Expired
- 1980-12-04 DE DE8080107595T patent/DE3062082D1/de not_active Expired
- 1980-12-04 AT AT80107595T patent/ATE2534T1/de not_active IP Right Cessation
- 1980-12-09 CA CA000366411A patent/CA1141750A/en not_active Expired
- 1980-12-09 HU HU802948A patent/HU182250B/hu not_active IP Right Cessation
- 1980-12-09 IE IE2571/80A patent/IE50611B1/en unknown
- 1980-12-10 JP JP17331680A patent/JPS5692900A/ja active Granted
- 1980-12-10 US US06/215,761 patent/US4315866A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DK515580A (da) | 1981-06-11 |
| DE2950026C2 (de) | 1982-05-19 |
| IE50611B1 (en) | 1986-05-28 |
| IE802571L (en) | 1981-06-10 |
| DE2950026B1 (de) | 1981-07-23 |
| CA1141750A (en) | 1983-02-22 |
| IL61601A (en) | 1984-09-30 |
| IL61601A0 (en) | 1981-01-30 |
| ATE2534T1 (de) | 1983-03-15 |
| DE3062082D1 (en) | 1983-03-24 |
| HU182250B (en) | 1983-12-28 |
| DK146097C (da) | 1983-12-05 |
| JPS5692900A (en) | 1981-07-27 |
| EP0030368B1 (de) | 1983-02-16 |
| EP0030368A1 (de) | 1981-06-17 |
| JPS6352640B2 (da) | 1988-10-19 |
| US4315866A (en) | 1982-02-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |