DE1080107B - Process for the production of 1,4-pregnadiene-11-‰, 17ª ‡, 21-triol-3, 20-dione-21-capronate (caproic acid ester of prednisolone) - Google Patents

Process for the production of 1,4-pregnadiene-11-‰, 17ª ‡, 21-triol-3, 20-dione-21-capronate (caproic acid ester of prednisolone)

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Publication number
DE1080107B
DE1080107B DESCH22241A DESC022241A DE1080107B DE 1080107 B DE1080107 B DE 1080107B DE SCH22241 A DESCH22241 A DE SCH22241A DE SC022241 A DESC022241 A DE SC022241A DE 1080107 B DE1080107 B DE 1080107B
Authority
DE
Germany
Prior art keywords
prednisolone
capronate
triol
dione
caproic acid
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
Application number
DESCH22241A
Other languages
German (de)
Inventor
Dr Emanuel Kaspar
Dr Wolfgang Hiersemann
Dr Martin Schenck
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Pharma AG
Original Assignee
Schering AG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Schering AG filed Critical Schering AG
Priority to DESCH22241A priority Critical patent/DE1080107B/en
Publication of DE1080107B publication Critical patent/DE1080107B/en
Pending legal-status Critical Current

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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 1,4-Pregnadien-lIP,17a,21-triol-3,20-dion-21-capronat (Capronsäureester des Prednisolons) Ein Ester des Prednisolons, in dem die 21ständige Hydroxylgruppe mit n-Capronsäure verestert ist, war bisher nicht bekannt.Process for the production of 1,4-pregnadiene-IIP, 17a, 21-triol-3,20-dione-21-capronate (Caproic acid ester of prednisolone) An ester of prednisolone in which the 21st Hydroxyl group is esterified with n-caproic acid, was not previously known.

Es wurde nun gefunden, daß dieser Ester, den man erfindungsgemäß durch partielle Veresterung des Prednisolons nach bekannten Verfahren, wie Umsetzung mit Anhydriden oder Halogeniden der Capronsäure, zweckmäßig in Gegenwart tertiärer Basen, erhält, sich durch eine im Vergleich zu den Estern der homologen Säuren auffallend hohe Löslichkeit in den zur intramuskulären Injektion geeigneten Lösungsmitteln, insbesondere in einem Gemisch von Müchsäureäthylester und Rizinusöl, auszeichnet.It has now been found that this ester, which is according to the invention by partial esterification of prednisolone by known processes, such as implementation with Anhydrides or halides of caproic acid, expediently in the presence of tertiary bases, obtained by a striking comparison with the esters of the homologous acids high solubility in solvents suitable for intramuscular injection, especially in a mixture of methyl ester and castor oil.

Dies ist aus der folgenden Tabelle der Löslichkeiten einiger homologer Prednisolonester, die in analoger Weise hergestellt werden, zu ersehen.This is from the following table of the solubilities of some homologous Prednisolone esters, which are prepared in an analogous manner, can be seen.

In je 1 ccm eines Gemisches von 3 Teilen Milchsäureäthylester und 1 Teil Rizinusöl lösen sich bei 22' C folgende Mengen (in mg) der betreffenden Verbindung: 1 1 F. 1 IalD Prednisolon .......................... 15 bis 20 Prednisolon-21-acetat ................. 5 bis 10 Prednisolon-21-butyrat ................ 5 bis 10 229 bis 233' C + 102' (Dioxan) Prednisolon-21-valerianat ............. 30 bis 35 202 bis 203,5' C + 110. (CHCI,) Prednisolon-21-capronat ............... 160 bis 175 184,5 bis 185' C + 109- (CHCI,) Prednisolon-21-önanthat .............. 15 bis 20 182 bis 183,5' C + 104- (CHC1,) Zur Bestimmung der Löslichkeiten wurden abgewogene Mengen des zu untersuchenden Esters mit je 1 ccm des Lösungsmittels in zugeschmolzenen Röhren bei der angegebenen Temperatur geschüttelt. Die angegebenen Zahlen bedeuten, daß hierbei die jeweils angegebene niedrigere Gewichtsmenge klar in Lösung geht, während bei der höheren Menge ein gerade noch erkennbarer Rest dauernd ungelöst bleibt.In each 1 ccm of a mixture of 3 parts of ethyl lactate and 1 part of castor oil, the following amounts (in mg) of the compound in question dissolve at 22 ° C: 1 1 F. 1 IalD Prednisolone .......................... 15 to 20 Prednisolone 21 acetate ................. 5 to 10 Prednisolone-21-butyrate ................ 5 to 10 229 to 233 'C + 102' (dioxane) Prednisolone-21-valerianate ............. 30 to 35 202 to 203.5 'C + 110. (CHCI,) Prednisolone-21-capronate ............... 160 to 175 184.5 to 185 'C + 109- (CHCI,) Prednisolone-21-oenanthate .............. 15 to 20 182 to 183.5 'C + 104- (CHC1,) To determine the solubilities, weighed amounts of the ester to be investigated were shaken with 1 ccm of the solvent in sealed tubes at the specified temperature. The figures given mean that the lower weight amount given in each case dissolves clearly, while with the higher amount a remainder that can just be recognized remains permanently undissolved.

Das Auftreten eines derart ausgeprägten Löslichkeitsmaxiinums beim Capronat war nicht vorherzusehen. Solche ausgezeichnet hohe Löslichkeit besitzt erhebliche technische Bedeutung für die Herstellung wertvoller Injektionspräparate des Prednisolons, wie sie von der praktischen Therapie neuerdings für die Anlegung von Hormondepots im Organismus benötigt werden.The occurrence of such a pronounced maximum solubility in Capronat could not be foreseen. Has such excellent high solubility considerable technical importance for the production of valuable injection preparations of prednisolone, as it has recently been used in practical therapy for the application of hormone depots in the organism are required.

- Beispiel 2,5 g Al,4-Pregnadien-llß,17a,21-triol-3,20-dion werden in 15 ccm Pyridin gelöst, mit 2,5 ccm Capronsäureanhydrid versetzt und 16 Stunden bei Raumtemperatur stehengelassen. Nun wird das Reaktionsgeinisch mit Wasser versetzt und mit Methylenchlorid gut ausgeschüttelt. Nach dem Waschen der Methylenchloridlösung mit 2 n-Salzsäure und Wasser wird nach dem Trocknen mit Natriums-ulfat die Lösung zur Trockne eingeengt und der Rückstand mit Pentan verrieben. Durch Absaugen des kristallinen Rückstandes und gutem Waschen desselben mit Pentan werden so 3,1 g an rohem AI-4-Pregnadien-11 ß,17a,21-triol-3,20-dion-21-capronat mit dem F. = 179 bis 182,5'C erhalten. Nach einmaligem Umkristallisieren aus Methanol schmilzt die Substanz bei 184,5 bis 185' C, [a]D + 109' (C H c13). - Example 2.5 g of Al, 4-pregnadiene-11ß, 17a, 21-triol-3,20-dione are dissolved in 15 cc of pyridine, 2.5 cc of caproic anhydride are added and the mixture is left to stand for 16 hours at room temperature. The reaction mixture is then mixed with water and extracted well with methylene chloride. After washing the methylene chloride solution with 2N hydrochloric acid and water, the solution is evaporated to dryness after drying with sodium sulfate and the residue is triturated with pentane. By suctioning off the crystalline residue and washing it thoroughly with pentane, 3.1 g of crude AI-4-pregnadiene-11β, 17a, 21-triol-3,20-dione-21-capronate with a F. = 179 bis 182.5'C obtained. After recrystallizing once from methanol, the substance melts at 184.5 to 185 'C, [a] D + 109' (C H c13).

Claims (1)

PATENTANSPRUCH: Verfahren zur Herstellung von 1,4-Pregnadienllß,17a,21-triol-3,20-dion-21-capronat (Capronsäureester des Prednisolons), dadurch geke=zeichnet, daß man Prednisolon in an sich bekannter Weise mit einem reaktionsfähigen Derivat der Capronsäure, vorzugsweise mit deren Anhydrid oder Halogeniden, zweckmäßig in Gegenwart tertiärer Basen, verestert. PATENT CLAIM: Process for the production of 1,4-Pregnadienllß, 17a, 21-triol-3,20-dione-21-capronate (caproic acid ester of prednisolone), characterized in that prednisolone is known in a manner known per se with a reactive derivative the caproic acid, preferably with its anhydride or halides, advantageously in the presence of tertiary bases, esterified.
DESCH22241A 1957-06-06 1957-06-06 Process for the production of 1,4-pregnadiene-11-‰, 17ª ‡, 21-triol-3, 20-dione-21-capronate (caproic acid ester of prednisolone) Pending DE1080107B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DESCH22241A DE1080107B (en) 1957-06-06 1957-06-06 Process for the production of 1,4-pregnadiene-11-‰, 17ª ‡, 21-triol-3, 20-dione-21-capronate (caproic acid ester of prednisolone)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DESCH22241A DE1080107B (en) 1957-06-06 1957-06-06 Process for the production of 1,4-pregnadiene-11-‰, 17ª ‡, 21-triol-3, 20-dione-21-capronate (caproic acid ester of prednisolone)

Publications (1)

Publication Number Publication Date
DE1080107B true DE1080107B (en) 1960-04-21

Family

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Application Number Title Priority Date Filing Date
DESCH22241A Pending DE1080107B (en) 1957-06-06 1957-06-06 Process for the production of 1,4-pregnadiene-11-‰, 17ª ‡, 21-triol-3, 20-dione-21-capronate (caproic acid ester of prednisolone)

Country Status (1)

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DE (1) DE1080107B (en)

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