CH257400A - Process for the preparation of a new oxy-octahydrophenanthrene derivative. - Google Patents
Process for the preparation of a new oxy-octahydrophenanthrene derivative.Info
- Publication number
- CH257400A CH257400A CH257400DA CH257400A CH 257400 A CH257400 A CH 257400A CH 257400D A CH257400D A CH 257400DA CH 257400 A CH257400 A CH 257400A
- Authority
- CH
- Switzerland
- Prior art keywords
- methyl
- ethyl
- phenanthrene
- octahydro
- carboxylic acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 238000002844 melting Methods 0.000 claims description 3
- 230000008018 melting Effects 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 230000001076 estrogenic effect Effects 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 206010067572 Oestrogenic effect Diseases 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 5
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- -1 ethylmagnesium halide Chemical class 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- PJDWNSYGMXODTB-UHFFFAOYSA-N 1,2,3,4,4a,4b,5,6-octahydrophenanthrene Chemical compound C1=CCCC2C(CCCC3)C3=CC=C21 PJDWNSYGMXODTB-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- WJGAPUXHSQQWQF-UHFFFAOYSA-N acetic acid;hydrochloride Chemical compound Cl.CC(O)=O WJGAPUXHSQQWQF-UHFFFAOYSA-N 0.000 description 1
- MNZMECMQTYGSOI-UHFFFAOYSA-N acetic acid;hydron;bromide Chemical compound Br.CC(O)=O MNZMECMQTYGSOI-UHFFFAOYSA-N 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/36—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by hydrogenation of carbon-to-carbon unsaturated bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/58—Preparation of carboxylic acid halides
- C07C51/60—Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides or esters, lactones, salts into halides with the same carboxylic acid part
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Verfahren zur Herstellung eines neuen Oxy-oetahydrophenanthren-Derivates. Es wurde gefunden, dass man zu einem neuen Oxy-octahydrophenanthren-Derivat ge langen kann, wenn man eine 1-Äthyl-2- niethyl -1,2,3,4,9,10,11,12 - octahydro - phen- aiithren - 2 -ca.rbonsä.ure, die in 7-Stellung einen, durch Hydrolyse in die Hydroxyl- gruppe überführbaren Substituenten, z. B.
eine verätherte oder veresterte Hydroxyl- wie eine Alhoxy- oder Acyloxygruppe, enthält., zwecks Bildung einer freien Hydroxylgruppe mit hy drolysierenden Mitteln behandelt.
Das noch nicht. bekannte Endprodukt des Verfahrens, die 1-Äthyl-2-methyl-7-oxy-1,2, 3,4,9,1.0,11,12 - octahydro- phenanthren -21-car- bonsäure vom F. 181 bis 182 , zeigt sowohl bei parenteraler als auch bei oraler Appli kation eine ausserordentlich hohe oestrogene -#Virlzi-ng. Es soll therapeutische Verwen dung finden oder als Zwischenprodulkt zur Herstellung therapeutisch verwendbarer Ver bindungen dienen.
Für die Hydrolyse des Substituenten in 7-Stellung verwendet man beispielsweise a.n- organische Basen, wie Alkali:- oder Erd- < illzalihy droxyde, Gemische organischer und anorganischer Säuren, wie Essigsäure-Salz- säure oder Essigsäure-Bromwasserstoffsäure, oder Salze organischer Basen mit anorgani schen Säuren, wie Pyridinhydrochlorid.
Die Ausgangsstoffe- werden zum Beispiel erhalten aus 1-Keto-2-methyl-1,2,3,4,9,10, 11,12 - octahydro - phenanthren-2-carbonsäure- estern, die in 7-Stellung einen durch Hydro lyse in die Hydroxylgruppe überführbaren Substituenten enthalten durch Grignardie- rung mit einem Äthylmagnesiumha.logenid, Wasserabspaltung aus dem erhaltenen Ca.r- binol,
Verseifung der veresterten Carboxyl- Gruppe und Hydrierung der Athy lendoppel- bindung.
<I>Beispiel:</I> 1 Gewichtsteil 1-Äthy 1- 2-methyl-7-methoxy 1,2,3,4,9,10,11,12 - octahydro -phenanthren.-2- carbonsäure vom F. 187 bis 188 und der Formel
EMI0001.0076
erhitzt man mit 10 Gewichtsteilen Pyridin- hydrochlorid während 3 bis 4 Stunden auf 170 M180 . Nach dem Erkalten wird Was ser zugegeben, mit Äther ausgeschüttelt und der Äther mit Salzsäure, Biocarbona.tlösung und Waseer gewaschen.
Der Rückstand der verdampften Ätherlösung liefert, nach Um- kristallisieren aus Essigester, die oestrogen wirksame 1- Äthyl - 2 - methyl-7-oxy-1,2,3,4, 9,10,11,121-octahydro-phenanthren; 2-carbon- säure vom F. 181 bis 182 der Formel
EMI0001.0089
Den Ausgangsstoff erhält man zum Bei spiel wie folgt:
6,5 Gewichtsteile 1-Keto-2- methyl - 7 - methoxy-1,2,3,4,9,10,11,12 - octa- hydro -phenanthren-2-carbonsäuremethylester vom F.
133 bis 135 lässt man mit einer Gri- gnardlösung, hergestellt aus. 0,6 Gewichtsteil Magnesium und 2 Volumteilen Äthylbromid, reagieren, erhitzt 6 Gewichtsteile des so er haltenen Carbinols zwecks Wasserabspaltung in einer Mischung von 6 Volumteilen Phos- phoroxychlorid und 60 Volumteilen Pyridin,
verseift die Carbonsäuremethylester-Gruppe durch Erhitzen von 5 Gewichtsteilen Was- serabspaltungsprodukt (1-Äthyliden - 2 -me thyl-7-methoxy-1,2,3,4,9,10,11,12.-,octahydro- phenanthren - 2 - carbonsäure-methylester) in einer Mischung von 10 Gewichtsteilen Ka- liumhydroxyd, 7,
5 Volumteilen Wasser und 15 Volumteilen Alkohol auf 160 und hy driert 2 Gewichtsteile der ungesättigten Säure in 200 Volumteilen Methanol in Ge genwart von 2 Gewiehtsteilen-eines Platin- katalysators zur 1-Äthyl-2-methyl-7-methoxy- 1,2,3,4,9,10,11,12 - octahydro@-phenanthren - 2- carbonsäure vom F. 187 bis 188 .
Process for the preparation of a new oxy-oetahydrophenanthrene derivative. It has been found that a new oxy-octahydrophenanthrene derivative can be obtained by using a 1-ethyl-2-ethyl-1,2,3,4,9,10,11,12-octahydro-phenanthrene - 2 -ca.rbonsä.ure, which has a substituent in the 7-position which can be converted into the hydroxyl group by hydrolysis, e.g. B.
an etherified or esterified hydroxyl such as an alhoxy or acyloxy group, contains., Treated for the purpose of forming a free hydroxyl group with hydrolyzing agents.
Not that yet. known end product of the process, the 1-ethyl-2-methyl-7-oxy-1,2, 3,4,9,1.0,11,12-octahydro- phenanthrene -21-carboxylic acid with a melting point of 181 to 182, shows an extraordinarily high oestrogenic - # Virlzi-ng with parenteral as well as with oral application. It should find therapeutic use or serve as an intermediate product for the production of therapeutically usable compounds.
For the hydrolysis of the substituent in the 7-position one uses, for example, inorganic bases, such as alkali: - or Erd- <illzalihy droxyde, mixtures of organic and inorganic acids, such as acetic acid-hydrochloric acid or acetic acid-hydrobromic acid, or salts of organic bases with inorganic acids such as pyridine hydrochloride.
The starting materials are obtained, for example, from 1-keto-2-methyl-1,2,3,4,9,10, 11,12-octahydro-phenanthrene-2-carboxylic acid esters which are in the 7-position by hydro lysis into the hydroxyl group convertible substituents contain by Grignardization with an ethylmagnesium halide, elimination of water from the Ca.rbinol obtained,
Saponification of the esterified carboxyl group and hydrogenation of the ethylene double bond.
<I> Example: </I> 1 part by weight of 1-Ethy 1- 2-methyl-7-methoxy 1,2,3,4,9,10,11,12 - octahydro-phenanthrene-2-carboxylic acid from F. 187 to 188 and the formula
EMI0001.0076
heated with 10 parts by weight of pyridine hydrochloride for 3 to 4 hours to 170 M180. After cooling, water is added, shaken out with ether and the ether is washed with hydrochloric acid, biocarbonate solution and water.
The residue of the evaporated ether solution gives, after recrystallization from ethyl acetate, the estrogenically active 1-ethyl-2-methyl-7-oxy-1,2,3,4, 9,10,11,121-octahydro-phenanthrene; 2-carboxylic acid with a melting point of 181 to 182 of the formula
EMI0001.0089
The starting material can be obtained as follows, for example:
6.5 parts by weight of 1-keto-2-methyl-7-methoxy-1,2,3,4,9,10,11,12-octa-hydro-phenanthrene-2-carboxylic acid methyl ester from F.
133 to 135 are left out with a Grignard solution. 0.6 part by weight of magnesium and 2 parts by volume of ethyl bromide, react, 6 parts by weight of the carbinol obtained in this way are heated for the purpose of splitting off water in a mixture of 6 parts by volume of phosphorus oxychloride and 60 parts by volume of pyridine,
the methyl carboxylate group is saponified by heating 5 parts by weight of water splitting product (1-ethylidene - 2-methyl-7-methoxy-1,2,3,4,9,10,11,12 .-, octahydro- phenanthrene - 2 - methyl carboxylate) in a mixture of 10 parts by weight of potassium hydroxide, 7,
5 parts by volume of water and 15 parts by volume of alcohol to 160 and hydrogenated 2 parts by weight of the unsaturated acid in 200 parts by volume of methanol in the presence of 2 parts by weight of a platinum catalyst to 1-ethyl-2-methyl-7-methoxy-1,2,3 , 4,9,10,11,12 - octahydro @ -phenanthrene - 2-carboxylic acid of mp 187-188.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH257400T | 1947-04-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH257400A true CH257400A (en) | 1948-10-15 |
Family
ID=4472158
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH257400D CH257400A (en) | 1947-04-24 | 1947-04-24 | Process for the preparation of a new oxy-octahydrophenanthrene derivative. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH257400A (en) |
-
1947
- 1947-04-24 CH CH257400D patent/CH257400A/en unknown
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