CH263483A - Process for the preparation of a new oxyhydrophenanthrene derivative. - Google Patents
Process for the preparation of a new oxyhydrophenanthrene derivative.Info
- Publication number
- CH263483A CH263483A CH263483DA CH263483A CH 263483 A CH263483 A CH 263483A CH 263483D A CH263483D A CH 263483DA CH 263483 A CH263483 A CH 263483A
- Authority
- CH
- Switzerland
- Prior art keywords
- carboxylic acid
- methyl
- phenanthrene
- tetrahydro
- oxyhydrophenanthrene
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title claims description 3
- 238000005984 hydrogenation reaction Methods 0.000 claims description 5
- -1 1-ethylidene-2-methyl-7-benzyloxy-1,2,3,4-tetrahydro-phenanthrene-2-carboxylic acid Chemical compound 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- 206010067572 Oestrogenic effect Diseases 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 230000001076 estrogenic effect Effects 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-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
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- XXFXTBNFFMQVKJ-UHFFFAOYSA-N [diphenyl(trityloxy)methyl]benzene Chemical group C=1C=CC=CC=1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)OC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XXFXTBNFFMQVKJ-UHFFFAOYSA-N 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C62/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C62/30—Unsaturated compounds
- C07C62/34—Unsaturated compounds containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C62/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C62/30—Unsaturated compounds
- C07C62/32—Unsaturated compounds containing hydroxy or O-metal groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
verfahren zur Herstellung eines neuen Oxyhydrophenanthren-Derivates. Es wurde gefunden, dass man zu einem neuen Oxyhydrophenanthren-Derivat gelan gen kann, wenn man eine 1-Äthyliden-2-me- thyl -1,2,3,4-tetrahy dro-phenant.hren-2-carbon- säure, die in 7-Stellung einen durch Hydrie rung in die Hydroxylgruppe überführbaren Substituenten, wie z.
B. eine Benzyläther- oder Triphenylmethyläthergruppe, enthält, durch Hydrierung in die 1-Äthyl-2-methy 1-7- oxy-1,2,3,4 - tetrahydro,-phenanthren-2-carbon- säure überführt. Das bisher nicht bekannte Endprodukt des Verfahrens vom F. 2041) zeigt sowohl bei parenteraler als auch bei oraler Applikation eine ausserordentlich hohe oestro- gene Wirkung. Es soll therapeutische Ver wendung finden oder als Zwischenprodukt.
zur Herstellung therapeutisch verwendbarer Verbindungen dienen.
Als Hydrierungsmittel verwendet man bei spielsweise katalytisch angeregten Wasser stoff in Gegenwart von Katalysatoren, wie z. B. Platin, Palladium, Nickel und derglei chen oder deren Oxyden oder Niederschlägen auf geeigneten Trägern.
Die Ausgangsstoffe werden z. B. erhalten aus 1-Keto-2-methyl-1,2,3,4-tetrahydro-pheii- anthren-2-carbonsäureestern, die in 7-Stellung einen durch Hydrierung in die Hy droxyl- gruppe überführbaren Substituenten enthal ten, durch Grignardierung mit einem Äthyl- magnesiumhalogenid, Wasserabspaltung aus dem erhaltenen Carbinol und Verseifung der Carbonsäureestergruppe. <I>Beispiel:
</I> 1 Gewichtsteil 1-Äthyliden-2-methyl-7-ben- zyloxy^-1,2,3,4-tetrahydro-phenanthren- 2-car- bonsäure der Formel
EMI0001.0047
wird in 10 Volumteilen 0,5@ iger wässeriger Natronlauge in Gegenwart von 1 Gewichtsteil eines Nickelkatalysators unter Wasserstoff geschüttelt.
Nach Aufnahme der für 2 Mol- äquivalente berechneten Menge Wasserstoff wird vom Katalysator abfilt.riert, die Oxy- säure mittels Mineralsäure ausgefällt und ab- genutscht. Der Filterrückstand liefert, nach Umkristallisieren aus Essigester, die oestrogen wirksame 1-Äthyl-2-methy 1-7-oxy -1,2,3,4-tetra- hydro-phenanthren-2-carbonsäure vom F. 204 und der Formel
EMI0001.0065
Den Ausgangsstoff erhält man z.
B. wie folgt: 6,5 Gewichtsteile 1-Keto-2-methyl-7-ben- zy loxy -1,2,3,4 - tetrahydro-phenanthren- 2-car- bonsäuremethylester lässt man mit einer Gri- gnardlösung, hergestellt aus 0,6 Gewichtstei- len Magnesium und 2 Volumteilen Äthylbro- mid, reagieren,
erwärmt 6 Gewichtsteile des so erhaltenen Carbinols zwecks Wasserabspal tung mit 25 Volumteilen Ameisensäure auf dem Wasserbad und verseift die Carbonsäure- methylestergruppe durch Erhitzen von 5 Ge wichtsteilen Wasserabspaltungsprodukt (1- Äthyliden.. 2 -methyl-7-benzyloxy-1,2,3,4-tetra- hydro-phenanthren-2-carbonsäuremethylester )
in einer Mischung von 10 Gewichtsteilen Ka- liumhydroxyd, 7,5 Volumteilen Wasser und 15 Volumteilen Alkohol auf 1600.
process for the preparation of a new oxyhydrophenanthrene derivative. It has been found that a new oxyhydrophenanthrene derivative can be obtained if a 1-ethylidene-2-methyl -1,2,3,4-tetrahydro-phenant.hrene-2-carboxylic acid, in the 7-position by hydrogenation convertible into the hydroxyl substituents such.
B. contains a benzyl ether or triphenylmethyl ether group, converted into 1-ethyl-2-methy 1-7-oxy-1,2,3,4-tetrahydro-phenanthrene-2-carboxylic acid by hydrogenation. The hitherto unknown end product of the process of F. 2041) shows an extraordinarily high estrogenic effect both on parenteral and on oral administration. It should find therapeutic use or as an intermediate.
serve to produce therapeutically useful compounds.
The hydrogenating agent used is, for example, catalytically excited hydrogen in the presence of catalysts, such as. B. platinum, palladium, nickel and the like surfaces or their oxides or precipitates on suitable carriers.
The starting materials are z. B. obtained from 1-keto-2-methyl-1,2,3,4-tetrahydro-pheii- anthrene-2-carboxylic acid esters which contain a substituent in the 7-position which can be converted into the hydroxyl group by hydrogenation Grignardation with an ethyl magnesium halide, elimination of water from the carbinol obtained and saponification of the carboxylic acid ester group. <I> example:
</I> 1 part by weight of 1-ethylidene-2-methyl-7-benzyloxy ^ -1,2,3,4-tetrahydro-phenanthrene-2-carboxylic acid of the formula
EMI0001.0047
is shaken under hydrogen in 10 parts by volume of 0.5 @ strength aqueous sodium hydroxide solution in the presence of 1 part by weight of a nickel catalyst.
After the amount of hydrogen calculated for 2 molar equivalents has been taken up, the catalyst is filtered off, the oxy acid is precipitated using mineral acid and suction filtered. The filter residue provides, after recrystallization from ethyl acetate, the estrogenically active 1-ethyl-2-methy 1-7-oxy -1,2,3,4-tetra-hydro-phenanthrene-2-carboxylic acid of F. 204 and the formula
EMI0001.0065
The starting material is obtained z.
B. as follows: 6.5 parts by weight of 1-keto-2-methyl-7-benzy loxy -1,2,3,4-tetrahydro-phenanthrene-2-carboxylic acid methyl ester are left with a Grignard solution from 0.6 parts by weight of magnesium and 2 parts by volume of ethyl bromide, react,
heats 6 parts by weight of the carbinol obtained in this way with 25 parts by volume of formic acid on a water bath for the purpose of dehydration and saponifies the methyl carboxylate group by heating 5 parts by weight of dehydration product (1- ethylidene .. 2-methyl-7-benzyloxy-1,2,3 4-tetra- hydro-phenanthrene-2-carboxylic acid methyl ester)
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 1600.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH263483T | 1944-01-10 | ||
| CH252529T | 1944-01-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH263483A true CH263483A (en) | 1949-08-31 |
Family
ID=25729613
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH263483D CH263483A (en) | 1944-01-10 | 1944-01-10 | Process for the preparation of a new oxyhydrophenanthrene derivative. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH263483A (en) |
-
1944
- 1944-01-10 CH CH263483D patent/CH263483A/en unknown
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