DE1047789B - Process for preparing the levorotatory 1,8-lactone of 6ª-bromo-8ª-oxy-2ª-methoxy-3ªª,5ª-oxido-7-oxo-9ª-10ª-decahydronaphthalene-1ª-carboxylic acid - Google Patents
Process for preparing the levorotatory 1,8-lactone of 6ª-bromo-8ª-oxy-2ª-methoxy-3ªª,5ª-oxido-7-oxo-9ª-10ª-decahydronaphthalene-1ª-carboxylic acidInfo
- Publication number
- DE1047789B DE1047789B DEL30403A DEL0030403A DE1047789B DE 1047789 B DE1047789 B DE 1047789B DE L30403 A DEL30403 A DE L30403A DE L0030403 A DEL0030403 A DE L0030403A DE 1047789 B DE1047789 B DE 1047789B
- Authority
- DE
- Germany
- Prior art keywords
- levorotatory
- decahydronaphthalene
- bromo
- methoxy
- lactone
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 238000004519 manufacturing process Methods 0.000 title claims 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
- 230000003647 oxidation Effects 0.000 claims description 12
- 238000007254 oxidation reaction Methods 0.000 claims description 12
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 8
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 claims description 6
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 claims description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 3
- 239000012074 organic phase Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 7
- 239000000203 mixture Substances 0.000 description 5
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- 206010042618 Surgical procedure repeated Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/30—Oxygen atoms, e.g. delta-lactones
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung des linksdrehenden 1,8-Lactons der 6 a-Brom-8ß-oxy-2 a-methoxy-3ß,5ß-oxido-'7-oxo-9 a-10 a-decahydronaphthalin-1 ß-carbonsäure Die Erfindung betrifft ein Verfahren zur Herstellung des linksdrehenden1,8-Lactons der 6a-Brom-Bß-oxy-2a-methoxy-3ß,5ß-oxido-7-oxo-9a-10a-decahydronaphthalin-lß-carbonsäure der Formel II durch Oxydation des linksdrehenden 1,8-Lactons der 6a-Brom-7ß,8ß-dioxy-2a-methoxy-3ß,5ß-oxido -9a-10a- decahydronaphthalin-1ß-carbonsäure der Formel I. Nach einem älteren Vorschlag wird die Oxydation der Verbindung I zur Verbindung II mittels Chromsäure in Gegenwart von Essigsäure durchgeführt, und die dabei erhalteneAusbeute an derVerbindung II, einemZwischenprodukt bei der Reserpinsynthese, erreicht etwa 74 °/o. Es wurde nun gefunden, daß man diese Ausbeute auf 90 bis 910/, erhöhen kann, wenn man die Oxydation mit einer Lösung von Chromsäure und Phosphorsäure in wäßriger Essigsäure bei gewöhnlicher Temperatur in Gegenwart eines mit Wasser nicht mischbaren Lösungsmittels, wie Dichloräthan,Tetrachloräthan oder Methylenchlorid, das gegenüber Chromsäure beständig ist, durchführt und das Oxydationsprodukt durch Abziehen und Eindampfen der organischen Phase abtrennt.Process for the preparation of the levorotatory 1,8-lactone of 6α-bromo-8β-oxy-2α-methoxy-3β, 5β-oxido-'7-oxo-9α-10α-decahydronaphthalene-1β-carboxylic acid. The invention relates to a process for the preparation of the levorotatory 1,8-lactone of 6a-bromo-Bß-oxy-2a-methoxy-3ß, 5ß-oxido-7-oxo-9a-10a-decahydronaphthalene-lß-carboxylic acid of the formula II by oxidation of the levorotatory 1,8-lactones of 6a-bromo-7ß, 8ß-dioxy-2a-methoxy-3ß, 5ß-oxido-9a-10a-decahydronaphthalene-1ß-carboxylic acid of the formula I. According to an older proposal, the oxidation of the compound I to the compound II is carried out by means of chromic acid in the presence of acetic acid, and the yield of the compound II, an intermediate product in the reserpine synthesis, thus obtained reaches about 74%. It has now been found that this yield can be increased to 90 to 910% if the oxidation is carried out with a solution of chromic acid and phosphoric acid in aqueous acetic acid at ordinary temperature in the presence of a water-immiscible solvent such as dichloroethane, tetrachloroethane or methylene chloride , which is resistant to chromic acid, and separates the oxidation product by stripping off and evaporating the organic phase.
Die Oxydation verläuft im allgemeinen dann besonders gut, wenn man das aus einer Lösung der theoretischen Menge Chromsäure und Phosporsäure in wäßriger Essigsäure bestehende Oxydationsgemisch in mehreren Anteilen einführt. Nach beendeter Oxydation trennt man die organische Phase ab, wäscht den Extrakt und dampft ihn zur Trockne ein. Die so erhaltene Säure der Formel II wird durch Kristallisieren aus einem organischen Lösugsmittel gereinigt.The oxidation generally proceeds particularly well when you that from a solution of the theoretical amount of chromic acid and phosphoric acid in aqueous Acetic acid introduces existing oxidation mixture in several proportions. After finished Oxidation, the organic phase is separated off, the extract is washed and evaporated dry up. The acid of the formula II thus obtained is crystallized purified from an organic solvent.
Das folgende Beispiel erläutert die Erfindung. Man kann auch das dritte Lösungsmittel, das von dem Oxydationsgemisch nicht angegriffen werden und eine leichte Trennung ermöglichen soll, ändern oder etwas unterhalb oder oberhalb gewöhnlicher Temperatur arbeiten, ohne aus dem Bereich der Erfindung zu gelangen. Beispiel Man führt 1 kg der Verbindung I und 2,51 Essigsäure unter mechanischem Rühren in 151 Dichloräthan ein. Zu der so erhaltenen Suspension gibt man unter starkem Rühren rasch 1,51 eines Oxydationsgemisches, das durch Auflösen von 700 g Chromsäure in 700 ccm Wasser und Zusatz von 620 ccm Phosphorsäure (55°Be) und 1200 ccm reiner Essigsäure erhalten worden ist, wobei man die Temperatur durch Außenkühlung bei etwa 20°C hält. Nach vollständiger Zugabe wird noch 30 Minuten bei 18 bis 20°C weitergekühlt. Die Verbindung I löst sich auf, und es bildet sich eine grünliche Emulsion, die man auf einmal mit 500 ccm des oben beschriebenen Oxydationsgemischs versetzt. Dann wird erneut i/2 Stunde bei der gleichen Temperatur gerührt und diese Arbeitsweise zur Einführung des Restes des Oxydationsgemischs noch zweimal wiederholt.The following example illustrates the invention. You can also do the third Solvent that is not attacked by the oxidation mixture and is a light one Separation is supposed to allow change or something below or above ordinary Working temperature without going out of the scope of the invention. Example man leads 1 kg of the compound I and 2.5 l of acetic acid to 151 with mechanical stirring Dichloroethane. The suspension thus obtained is added with vigorous stirring quickly 1.51 of an oxidation mixture obtained by dissolving 700 g of chromic acid in 700 cc of water and the addition of 620 cc of phosphoric acid (55 ° Be) and 1200 cc of purer Acetic acid has been obtained, the temperature being increased by external cooling at holds around 20 ° C. After the addition is complete, cooling is continued at 18 to 20 ° C. for a further 30 minutes. The compound I dissolves and a greenish emulsion forms, the 500 cc of the oxidation mixture described above are added all at once. then is stirred again for 1/2 hour at the same temperature and this procedure Repeated twice more to introduce the remainder of the oxidation mixture.
Man läßt stehen und überführt dann in einen Scheidetrichter oder eine ähnliche Vorrichtung. Die Dichdoräthan-Schicht wird mehrere Male mit Wasser gewaschen, und die Waschwässer werden mehrere Male mit Dichloräthan extrahiert. Die bei der zweiten Extraktion erhaltenen Dichloräthan-Anteile werden vereinigt, mit Nassei gewaschen und dann mit dem ersten Dichloräthan-Extrakt vereinigt. Die vereinigten Extrakte werden über Magnesiumsulfat getrocknet, abfiltriert und im Vakuum zur Trockne eingedampft. Der aus der gesuchten Verbindung II bestehende Rückstand wird mit Essigsäureäthylester aufgenommen, den man dann zum Abschleppen des Dichloräthans abdestilliert. Der in einem halben Volumen Essigsäureäthylester aufgenommene Rückstand liefert nach dem Kristallisieren bei tiefer Temperatur, Absaugen, Waschen mit auf -10 bis -15°C abgekühltem Essigsäureäthylester, Absaugen und Trocknen 900 g der gesuchten Verbindung II vom F. 151 bis 152°C und [a] ö° = 245 bis 255°C (c = 10/0 in Tetrahydrofuran).It is left to stand and then transferred to a separating funnel or a similar device. The dichloroethane layer is washed several times with water, and the wash waters are extracted several times with dichloroethane. The at the Second extraction obtained dichloroethane portions are combined with wet egg washed and then combined with the first dichloroethane extract. The combined extracts are dried over magnesium sulfate, filtered off and evaporated to dryness in vacuo. The one consisting of the wanted compound II The residue is taken up in ethyl acetate, which is then towed away of the dichloroethane distilled off. In half a volume of ethyl acetate absorbed residue gives after crystallization at low temperature, suction, Washing with ethyl acetate cooled to -10 to -15 ° C, suction and drying 900 g of the desired compound II with a temperature of 151 to 152 ° C and [a] ö ° = 245 to 255 ° C (c = 10/0 in tetrahydrofuran).
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR1047789X | 1957-06-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1047789B true DE1047789B (en) | 1958-12-31 |
Family
ID=9593041
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEL30403A Pending DE1047789B (en) | 1957-06-17 | 1958-05-14 | Process for preparing the levorotatory 1,8-lactone of 6ª-bromo-8ª-oxy-2ª-methoxy-3ªª,5ª-oxido-7-oxo-9ª-10ª-decahydronaphthalene-1ª-carboxylic acid |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1047789B (en) |
-
1958
- 1958-05-14 DE DEL30403A patent/DE1047789B/en active Pending
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