CH258192A - Process for the preparation of a new oxyhydrophenanthrene derivative. - Google Patents
Process for the preparation of a new oxyhydrophenanthrene derivative.Info
- Publication number
- CH258192A CH258192A CH258192DA CH258192A CH 258192 A CH258192 A CH 258192A CH 258192D A CH258192D A CH 258192DA CH 258192 A CH258192 A CH 258192A
- Authority
- CH
- Switzerland
- Prior art keywords
- phenanthrene
- hexahydro
- methyl
- carboxylic acid
- ethyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title claims description 4
- -1 1-ethyl-2-methyl-7-benzoyl-oxy -1,2,3,4,9,10-hexahydro-phenanthrene-2-carboxylic acid methyl ester Chemical compound 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 206010067572 Oestrogenic effect Diseases 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 230000001076 estrogenic effect Effects 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 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
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- RVAKYIUFDWMFMI-UHFFFAOYSA-N methyl 7-methoxy-2-methyl-1-oxo-3,4,9,10-tetrahydrophenanthrene-2-carboxylate Chemical compound COC1=CC=C2C=3CCC(C(C3CCC2=C1)=O)(C)C(=O)OC RVAKYIUFDWMFMI-UHFFFAOYSA-N 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- IXZTWPINJVWVSW-UHFFFAOYSA-N 1,2,3,4,9,10-hexahydrophenanthrene-2-carboxylic acid Chemical compound C1=CC=C2C(CCC(C3)C(=O)O)=C3CCC2=C1 IXZTWPINJVWVSW-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- ATXRQOKSTOTYJH-UHFFFAOYSA-N methyl phenanthrene-2-carboxylate Chemical compound C1=CC=C2C3=CC=C(C(=O)OC)C=C3C=CC2=C1 ATXRQOKSTOTYJH-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture 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
- 230000007017 scission Effects 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Verfahren zur Herstellung eines neuen Oxyhydrophenanthren-Derivates. Es wurde gefunden, daB man zu einem neuen Oxyhydrophenanthren-Derivat gelan gen kann, wenn man den 1-Äthyl-2-methyl 7-oxy,1,2,3,4,9,10-hexahydro-phenanthren-2- carbonsäuremethylester mit einem verestern- den Mittel behandelt, das die Hydroxyl- gruppe in 7-Stellung in die Benzoyloxy- gruppe überführt.
Das noch nicht bekannte Endprodukt des Verfahrens, der 1-Äthyl-2-methyl-7-benzoyl- oxy-1,2,3,4,9,10 -hexahydro-phenanthren- 2 - carbonsäuremethylester, zeigt sowohl bei par- enteraler als auch bei oraler Applikation eine ausserordentlich hohe oestrogene Wirkung. Es soll therapeutische Verwendung finden oder. als Zwischenprodukt zur Herstellung thera peutisch verwendbarer Verbindungen dienen.
Für die Überführung der Hydrogylgruppe in 7-Stell'ung in die Benzoyloxygruppe ver wendet man Benzoesäure bzw. ihre Derivate, wie z. B. Benzoylchlorid. Vorteilhaft arbeitet man in Gegenwart von Kondensationsmitteln und/oder Katalysatoren.
Der Ausgangsstoff wird z. B. erhalten aus dem 1- Keto - 2 - methyl - 7 - methoxy- 1, 2 , 3 , 4 , 9 ,10 - hexahydro - phenanthren - 2 - carbonsäuremethylester durch Grignardierung mit einem Äthylmagnesiumhalogend, Isolie rung des so erhaltenen 1-Äthyliden-2-methyl-7 methoxy-1,2,3,4,9,10-hexahydro-phenanthren- 2-carbonsäuremethylesters,
Hydrierung der Athyliden-Doppelbindung und anschliessende Spaltung der 7-Methoxygruppe unter Bil dung des 1-Äthyl-2-methyl-7-oxy-1,2, 3,4,9,10- hexahydro-phenanth ren-2-carbonsäuremethyl- esters.
<I>Beispiel:</I> 1 Gewichtsteil 1-Äthyl-2-methyl-7-oxy- 1, 2, 3,4, 9,10-hexahydro-phenauthren-2-carbon- säuremethylester der Formel
EMI0001.0059
wird in einer Mischung von 10 Volumteilen Pyridin und 5 Volumteilen Benzoyl'chlorid 24 Stunden bei Raumtemperatur stehen ge lassen. Hierauf wird Wasser zugegeben, mit Äther ausgeschüttelt und der Äther mit Salz säure, BikarbonaIlösung und Wasser ge waschen.
Der Rückstand der verdampften Ätherlösung liefert, nach Umkristallisieren aus Alkohol, den oestrogen wirksamen 1-Äthyl - 2 - methyl-7-benzoyloxy -1, 2, 3,4, 9,10 hexahydro-phenanthren-2-carbonsäuremethyl- ester der Formel
EMI0001.0075
Den Ausgangsstoff erhält man z.
B. wie folgt: 12 Gewichtsteile 1-Keto-2-methyl-7 methoxy-1,2,3,4,9,10-hexahydro-phenanthren- 2-carbonsäumemethylester lässt man mit einer Grignardlösung, hergestellt aus. 1,25 Ge wichtsteilen Magnesium und 5 Vol'umteilen Äthyljodid, reagieren, isoliert den so ent standenen 1-Äthyliden-2-methyl-1,2,3,4,9,10 hexahydro=phenanthren-2-carbonsäuremethyl- ester vom F.
146-147 , hydriert 1 Gewichts- teil der Athyliden-Verbinflung in 30 Volum- teilen Alkohol in Gegenwart von 1 Gewichts- teil eines zum 1-Athyl-2- methyl --7 - methoxy -1,2,3,4,9,10 - hexahydra- phenanthren - 2 - carbons-äureme#thylester vom F.
77-79 und spaltet anschliessend die 7-Methoxygruppedurch kurzes Erhitzen von 1 Gewichtsteil der letzteren Verbindung mit 10 Gewichtsteilen Pyridinhydrochlorid.
Process for the preparation of a new oxyhydrophenanthrene derivative. It has been found that a new oxyhydrophenanthrene derivative can be obtained if methyl 1-ethyl-2-methyl 7-oxy, 1,2,3,4,9,10-hexahydro-phenanthrene-2-carboxylate is used treated with an esterifying agent that converts the hydroxyl group in the 7-position into the benzoyloxy group.
The not yet known end product of the process, the 1-ethyl-2-methyl-7-benzoyl-oxy-1,2,3,4,9,10-hexahydro-phenanthrene-2-carboxylic acid methyl ester, shows both parenteral and an extraordinarily high estrogenic effect even with oral administration. It should find therapeutic use or. serve as an intermediate for the preparation of therapeutically usable compounds.
For the conversion of the hydrogyl group in the 7-Stell'position into the benzoyloxy group ver use benzoic acid or its derivatives, such as. B. benzoyl chloride. It is advantageous to work in the presence of condensing agents and / or catalysts.
The starting material is z. B. obtained from the 1 - keto - 2 - methyl - 7 - methoxy - 1, 2, 3, 4, 9, 10 - hexahydro - phenanthrene - 2 - carboxylic acid methyl ester by Grignardation with an ethylmagnesium halogen, isolation of the 1-ethylidene thus obtained -2-methyl-7 methoxy-1,2,3,4,9,10-hexahydro-phenanthrene-2-carboxylic acid methyl ester,
Hydrogenation of the ethylidene double bond and subsequent cleavage of the 7-methoxy group with formation of the 1-ethyl-2-methyl-7-oxy-1,2, 3,4,9,10-hexahydro-phenanthrene-2-carboxylic acid methyl ester .
<I> Example: </I> 1 part by weight of 1-ethyl-2-methyl-7-oxy-1, 2, 3,4, 9,10-hexahydro-phenauthrene-2-carboxylic acid methyl ester of the formula
EMI0001.0059
is left to stand ge in a mixture of 10 parts by volume of pyridine and 5 parts by volume of benzoyl chloride for 24 hours at room temperature. Then water is added, extracted with ether and the ether is washed with hydrochloric acid, bicarbonate solution and water.
The residue of the evaporated ether solution gives, after recrystallization from alcohol, the estrogenically active 1-ethyl-2-methyl-7-benzoyloxy-1, 2, 3,4, 9,10 hexahydro-phenanthrene-2-carboxylic acid methyl ester of the formula
EMI0001.0075
The starting material is obtained z.
B. as follows: 12 parts by weight of 1-keto-2-methyl-7-methoxy-1,2,3,4,9,10-hexahydro-phenanthrene-2-carboxylic acid methyl ester are left with a Grignard solution. 1.25 parts by weight of magnesium and 5 parts by volume of ethyl iodide react, isolating the 1-ethylidene-2-methyl-1,2,3,4,9,10 hexahydro = phenanthrene-2-carboxylic acid methyl ester from F. .
146-147, hydrogenated 1 part by weight of the ethylidene compound in 30 parts by volume of alcohol in the presence of 1 part by weight of one to 1-ethyl-2-methyl -7-methoxy -1,2,3,4,9 , 10 - hexahydra- phenanthrene - 2 - carboxylic acids # thyl esters from F.
77-79 and then cleaves the 7-methoxy group by briefly heating 1 part by weight of the latter compound with 10 parts by weight of pyridine hydrochloride.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH250373T | 1944-01-10 | ||
| CH258192T | 1944-01-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH258192A true CH258192A (en) | 1948-11-15 |
Family
ID=25729448
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH258192D CH258192A (en) | 1944-01-10 | 1944-01-10 | Process for the preparation of a new oxyhydrophenanthrene derivative. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH258192A (en) |
-
1944
- 1944-01-10 CH CH258192D patent/CH258192A/en unknown
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