DE1146878B - Process for the preparation of new hydroxycarboxylic acid esters of the Pregnan range - Google Patents
Process for the preparation of new hydroxycarboxylic acid esters of the Pregnan rangeInfo
- Publication number
- DE1146878B DE1146878B DEF31968A DEF0031968A DE1146878B DE 1146878 B DE1146878 B DE 1146878B DE F31968 A DEF31968 A DE F31968A DE F0031968 A DEF0031968 A DE F0031968A DE 1146878 B DE1146878 B DE 1146878B
- Authority
- DE
- Germany
- Prior art keywords
- acid esters
- new
- pregnan
- hydroxycarboxylic acid
- preparation
- 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
Classifications
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Description
Verfahren zur Herstellung von neuen Hydroxycarbonsäureestern der Pregnanreihe Gegenstand des Hauptpatentes 1090 660 ist ein Verfahren zur Herstellung von neuen 21-Hydroxycarbonsäureestern der Pregnanreihe, das dadurch gekennzeichnet ist, daß man 21-Halogenderivate von Verbindungen der Pregnanreihe in Gegenwart eines inerten organischen Lösungsmittels oder Suspendierungsmittels mit Alkalisalzen von Hydroxycarbonsäuren umsetzt.Process for the production of new hydroxycarboxylic acid esters of the Pregnan series The subject of the main patent 1090 660 is a process for the production of new 21-Hydroxycarboxylic acid esters of the Pregnan series, which is characterized in that 21-halogen derivatives of compounds of the Pregnan series in the presence of an inert organic solvent or suspending agent with alkali salts of hydroxycarboxylic acids.
Es wurde nun gefunden, daß man derartige Steroid-21-hydroxycarbonsäureester in guten Ausbeuten auch dadurch erhält, daß man 21-Sulfonsäureester der 21-Hydroxypregnanreihe in Gegenwart eines inerten organischen Lösungs- oder Suspendierungsmittels, vorzugsweise in Dimethylformamid, mit Alkalisalzen von Hydroxycarbonsäuren umsetzt.It has now been found that such steroid 21-hydroxycarboxylic acid esters can be obtained Also obtained in good yields by 21-sulfonic acid esters of the 21-hydroxypregnane series in the presence of an inert organic solvent or suspending agent, preferably in dimethylformamide, with alkali metal salts of hydroxycarboxylic acids.
Die erfindungsgemäß zu verwendenden Alkalisalze der Hydroxycarbonsäuren sind dadurch erhältlich, daß man ein Alkalialkoholat in einem Lösungsmittel, z. B. Methanol oder Äthanol, im Molverhältnis 1 : 1 mit der entsprechenden Hydroxycarbonsäure zusammengibt und aus diesem Reaktionsgemisch mit einem inerten Lösungsmittel wie Aceton, Benzol, Tetrahydrofuran oder Dioxan das Alkalisalz ausfällt. Das Alkalisalz wird gut im Vakuum getrocknet und in einer Kugelmühle pulverisiert.The alkali metal salts of the hydroxycarboxylic acids to be used according to the invention can be obtained by adding an alkali metal alcoholate in a solvent, e.g. B. methanol or ethanol, in a molar ratio of 1: 1 with the corresponding hydroxycarboxylic acid and precipitates the alkali salt from this reaction mixture with an inert solvent such as acetone, benzene, tetrahydrofuran or dioxane. The alkali salt is dried well in vacuo and pulverized in a ball mill.
Als 21-Sulfonsäureester von 21-Hydroxysteroiden verwendet man zweckmäßig die Mesylate, jedoch sind auch Tosylate und Benzolsulfonate für die Reaktion geeignet. Als Steroidsulfonsäureester kommen z. B. folgende in Betracht: A 4-Pregnen-21-ol-3,20-dion-21-mesylat, A 4-Pregnen- 1 7oc,21-diol-3,11,20-trion-21-mesylat, A 4-Pregnen- 17oc,21 -diol-3,11,20-trion-21-tosylat, 6oc-Methyl-A 1,4-pregnadien-1 Iß, 17a,21-triol-3,20-dion-2 1 -mesylat, A 4_Pregnen- 1 Iß, 17,x-21 -triol-3,20-dion-2 1-mesylat, A 1, 4-Pregnen- 1 Iß, 1 7o#,21 -triol-3,20-dion. Die Veresterung erfolgt zweckmäßig, indem man die Sulfonsäureester der Steroide in Acetonitril, Dimethylsulfon, vorteilhaft in Dimethylformamid löst oder suspendiert und mit dem Alkalisalz der Hydroxycarbonsäure unter Rühren erwärmt. Man verwendet vorzugsweise einen geringen Überschuß an Alkalisalz. Die Reaktionszeit beträgt im allgemeinen 1 bis 5 Stunden, am besten jedoch 21/, Stunden. Die Reaktionstemperatur liegt im allgemeinen zwischen 30 und 100'C, insbesondere sind Temperaturen um 60'C geeignet.The mesylates are expediently used as 21-sulfonic acid esters of 21-hydroxysteroids, but tosylates and benzenesulfonates are also suitable for the reaction. As steroid sulfonic acid esters, for. B., the following: A 4-pregnene-21-ol-3,20-dione 21-mesylate, A 4-pregnen 7oC 1, 21-diol-3,11,20-trione 21-mesylate, A 4-pregnene-17oc, 21-diol-3,11,20-trione-21-tosylate, 6oc-methyl-A 1,4-pregnadiene-1β, 17a, 21-triol-3,20-dione-2 1 -mesylate, A 4_Pregnen- 1 Iß, 17, x-21 -triol-3,20-dione-2 1-mesylate, A 1, 4-pregnen- 1 Iß, 1 7o #, 21 -triol-3.20- dion. The esterification is expediently carried out by dissolving or suspending the sulfonic acid esters of the steroids in acetonitrile, dimethyl sulfone, advantageously in dimethylformamide, and heating them with the alkali metal salt of the hydroxycarboxylic acid with stirring. A slight excess of alkali salt is preferably used. The reaction time is generally 1 to 5 hours, but best 21 /, hours. The reaction temperature is generally between 30 and 100.degree. C., temperatures around 60.degree . C. are particularly suitable.
Als Hydroxycarbonsäuren kommen insbesondere die Abkömmlinge der Rizinolsäure und der Stearinsäure sowie andere längerkettige (C, bis C") Hydroxyfettsäuren in Frage. Beispiel 1 6cc-Methyl-A 1, 4-pregnadien- 1 Iß, 17oc,2 1 -triol-3,20-dion-12'-hydroxystearat-(21) Eine innige Mischung aus 4,52 g 6oc-Methyl-A 1, 4_pregnadien- 1 Iß, 17oc,21 -triol-3,20-dion-21 -mesylat und 4,23 g Kaliumsalz der 12'-Hydroxystearinsäure werden in 50 ml Dimethylformamid suspendiert und 21/, Stunden in einer Stickstoffatmosphäre und unter Rühren auf 60'C erwärmt. Das Reaktionsgemisch wird anschließend in 300 ml Wasser eingerührt. Der Ester wird mit Methylenchlorid-Äther extrahiert und nach dem Abdampfen des Lösungsmittels durch Zugabe von Petroläther zur Kristallisation gebracht.As hydroxycarboxylic acids are, in particular the derivatives of ricinoleic acid and of stearic acid, and other long-chain (C, to C ") hydroxy fatty acids in question. Example 1 6cc-methyl-A 1, 4-pregnadiene 1 Eat, 17oc, 2 1-triol-3, 20-dione-12'-hydroxystearate- (21) An intimate mixture of 4.52 g of 6oc-methyl-A 1, 4_pregnadien- 1 Iß, 17oc, 21-triol-3,20-dione-21-mesylate and 4, 23 g of the potassium salt of 12'-hydroxystearic acid are suspended in 50 ml of dimethylformamide and heated for 21 1/2 hours in a nitrogen atmosphere and with stirring to 60 ° C. The reaction mixture is then stirred into 300 ml of water after evaporation of the solvent brought to crystallization by adding petroleum ether.
Es werden so 6,1 g 6#x-Methyl-A 1, 4-pregnadien-1 Iß,17cc,21-triol-3,20-dion-12'-hydroxystearat-(21) vom Fp. 87'C (Kofler-Schmelzbank) erhalten.This gives 6.1 g of 6 # x-methyl-A 1, 4-pregnadiene-1 Iß, 17cc, 21-triol-3,20-dione-12'-hydroxystearate (21) with a melting point of 87'C ( Kofler melting bank).
Beispiel 2 A4mPregnen-21-ol-3,20-dion-12'-hydroxystearat-(21) 4,02 g A4_Pregnen-21-ol-3,20-dion-21-mesylat und 4,20g 12'-Hydroxystearinsäurekaliumsalz werden gut vermischt, mit 50 ml Dimethylformamid versetzt und 31/2 Stunden unter Rühren und in einer Stickstoffatmosphäre auf 60'C erwärmt. Nach dem Abkühlen des Reaktionsgemisches wird in 300 ml Wasser ein-; gerührt. Der entstandene Ester wird mit 3 - 25 ml Äther extrahiert. Nach dem Trocknen über Natriumsulfat wird der Extrakt im Vakuum und zum Schluß im Hochvakuum bei gO'C zur Trockne eingeengt.Example 2 A4mPregnen-21-ol-3,20-dione-12'-hydroxystearate- (21) 4.02 g A4_Pregnen-21-ol-3,20-dione-21-mesylate and 4.20 g of 12'-hydroxystearic acid potassium salt mixed well, mixed with 50 ml of dimethylformamide and heated to 60 ° C. for 31/2 hours with stirring and in a nitrogen atmosphere. After the reaction mixture has cooled, it is poured into 300 ml of water; touched. The resulting ester is extracted with 3 - 25 ml of ether. After drying over sodium sulfate, the extract is concentrated to dryness in vacuo and finally in a high vacuum at gO'C.
Es werden so 5,7g A4-Pregnen-21-ol-3,20-dion-12'-hydroxystearat-(21) als Öl erhalten.This gives 5.7 g of A4-pregnen-21-ol-3,20-dione-12'-hydroxystearate (21) as an oil .
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DEF31968A DE1146878B (en) | 1960-08-25 | 1960-08-25 | Process for the preparation of new hydroxycarboxylic acid esters of the Pregnan range |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DEF31968A DE1146878B (en) | 1960-08-25 | 1960-08-25 | Process for the preparation of new hydroxycarboxylic acid esters of the Pregnan range |
Publications (1)
Publication Number | Publication Date |
---|---|
DE1146878B true DE1146878B (en) | 1963-04-11 |
Family
ID=7094432
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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DEF31968A Pending DE1146878B (en) | 1960-08-25 | 1960-08-25 | Process for the preparation of new hydroxycarboxylic acid esters of the Pregnan range |
Country Status (1)
Country | Link |
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DE (1) | DE1146878B (en) |
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1960
- 1960-08-25 DE DEF31968A patent/DE1146878B/en active Pending
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