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CH331057A - Process for the preparation of basic benzilic acid esters - Google Patents

Process for the preparation of basic benzilic acid esters

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Publication number
CH331057A
CH331057ACH331057DACH331057ACH 331057 ACH331057 ACH 331057ACH 331057D ACH331057D ACH 331057DACH 331057 ACH331057 ACH 331057A
Authority
CH
Switzerland
Prior art keywords
acid
benzilic acid
basic
preparation
acid esters
Prior art date
Application number
Other languages
German (de)
Inventor
Gustav Dr Ehrhart
Ott Heinrich
Original Assignee
Hoechst 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 Hoechst AgfiledCriticalHoechst Ag
Publication of CH331057ApublicationCriticalpatent/CH331057A/en

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Translated fromGerman

   <Desc/Clms Page number 1>  Verfahren    zur      Herstellung   von    basischen      Benzilsäureestern   Es ist bereits bekannt, dass    Dialkylamino-      alkylester   der    Benzilsäure   pharmazeutisch wertvolle    Eigensehaften   besitzen    (AP   2399736,    AP   2401219 und    AP   2570181).   Es wurde gefunden, dass man durch Umsetzung von    Benzilsäure   oder deren funktionellen Derivaten mit    N-Alkyl-4-oxy-piperidi-      nen,   deren    Alkylgruppe   bis zu 4 Kohlenstoffatome enthält und deren    Piperidinkern   keine weiteren    Substituenten   trägt, pharmazeutisch wertvolle    Benzilsäure-N-alkyl-piperidyl-(4)-      ester   herstellen kann.   Die neuen Verbindungen zeichnen sich insbesondere durch gute    spasmolytische   Wirksamkeit bei geringer Toxizität aus. Beispielsweise entspricht die    spasmolytische   Wirksamkeit des    Benzilsäure-N-methyl-piperidyl-(4)-      esters,   wie am isolierten    Meerschweinchen-      Diekdarm   nach Tontraktion mit    Lentin   festgestellt wurde, etwa der dreifachen Wirkung des    Atropins;   dabei besitzt die Verbindung nur    1/3   der Toxizität des    Atropins.     Die erhaltenen Verbindungen lassen sich mit Hilfe von anorganischen oder organischen Säuren in die entsprechenden Salze überführen. Als anorganische Säuren kommen beispielsweise    Halogenwasserstoffsäuren,   Phosphorsäure, Schwefelsäure und    Amidosulfon-      säure   in Betracht. Als organische Säuren können beispielsweise    Oxalsäure,   Essigsäure, Milchsäure,. Bernsteinsäure,    .Maleirisäüre,      Apfelsäüre,   Weinsäure,    Salicylsäure,      Zitro-      nensäure,      Oxyäthansulfonsäure,      Acetursäure   und    Äthylendiamintetraessigsäure   verwendet werden.   Beispiel 1 25,6 g    Benzilsäureäthylester,   12 g    N-      1@Iethyl-4-oxypiperidin   und eine Lösung von 0,5g Natrium in 10    em3   absolutem    Alkohol   werden gemischt und die Mischung    2i/2   Stunden unter 80 mm Druck auf 110-120  C erhitzt. Nach dem Abkühlen wird in    verdünnter      Salzsäure   gelöst und die klare Lösung mit Soda alkalisch gemacht,    wobei   der    Benzil-      säure-N-methyl-piperidyl-(4)-ester   ausfällt. Ausbeute 22 g, F. = 164 C. F des    Chlor-      hydrates   = 209-210  C.   Beispiel 2 Zu einer Lösung von 1,5g Natrium in 60    em3   absolutem Äthanol werden 73 g    Benzil-   ;    säuremethylester   und 39 g    N-Äthyl-4-oxy-      piperidin   hinzugegeben. Das Reaktionsgemisch wird 5 Stunden unter 80 mm Druck auf 110-120  C erhitzt und nach dem Abkühlen in verdünnter Salzsäure gelöst. Anschliessend wird    ausgeäthert   und die    wässrige   Lösung mit Pottasche alkalisch gemacht, wobei der    Benzil-      säure-N-äthyl-piperidyl-(4)-ester   ausfällt. Ausbeute 50 g,    Schmelzpunkt   93  C (nach    Um-      kristallisieren   aus    Diisopr      opyläther)   .   Das  <Desc/Clms Page number 2>  Chlorhydrat schmilzt bei 1$2  C (nach    Um-      kristallisieren   aus    Acetonitril).   <Desc / Clms Page number 1> Process for the preparation of basic benzilic acid esters It is already known that dialkylaminoalkyl esters of benzilic acid have pharmaceutically valuable properties (AP 2399736, AP 2401219 and AP 2570181).  It has been found that reacting benzilic acid or its functional derivatives with N-alkyl-4-oxy-piperidines whose alkyl group contains up to 4 carbon atoms and whose piperidine nucleus carries no further substituents, pharmaceutically valuable benzilic acid-N-alkyl piperidyl (4) - ester can produce.  The new compounds are distinguished in particular by good spasmolytic effectiveness with low toxicity. For example, the spasmolytic activity of benzilic acid-N-methyl-piperidyl- (4) - ester, as was found on the isolated guinea pig bowel after traction with lentin, is approximately three times as effective as atropine; the compound has only 1/3 the toxicity of atropine.  The compounds obtained can be converted into the corresponding salts with the aid of inorganic or organic acids. Inorganic acids that can be used are, for example, hydrohalic acids, phosphoric acid, sulfuric acid and amidosulfonic acid. As organic acids, for example, oxalic acid, acetic acid, lactic acid,. Succinic acid, maleic acid, malic acid, tartaric acid, salicylic acid, citric acid, oxyethane sulfonic acid, aceturic acid and ethylenediaminetetraacetic acid can be used.  EXAMPLE 1 25.6 g of ethyl benzilate, 12 g of N-1 @ methyl-4-oxypiperidine and a solution of 0.5 g of sodium in 10 cubic meters of absolute alcohol are mixed and the mixture is heated to 110-120 ° C. for 2½ hours under 80 mm pressure heated. After cooling, it is dissolved in dilute hydrochloric acid and the clear solution is made alkaline with soda, whereupon the benzilic acid N-methyl-piperidyl (4) ester precipitates. Yield 22 g, F. = 164 C. F. of the chlorohydrate = 209-210 C.  Example 2 To a solution of 1.5 g of sodium in 60 cubic meters of absolute ethanol, 73 g of benzil; acid methyl ester and 39 g of N-ethyl-4-oxypiperidine are added. The reaction mixture is heated to 110-120 ° C. under 80 mm pressure for 5 hours and, after cooling, dissolved in dilute hydrochloric acid. It is then extracted with ether and the aqueous solution is made alkaline with potash, the benzilic acid N-ethyl-piperidyl (4) ester precipitating out. Yield 50 g, melting point 93 ° C. (after recrystallization from diisopropyl ether).   The <Desc / Clms Page number 2> Chlorohydrate melts at 12 ° C (after recrystallization from acetonitrile).

Claims (1)

Translated fromGerman
PATENTANSPRUCH Verfahren zur Hertellung von Benzilsäure- N-alkyl-piperidyl-(4)-estern, dadurch gekennzeichnet, dass man Benzilsäure oder deren funktionelle Derivate mit N-Alkyl-4-o.xy- piperidinen, deren Alkylgruppe bis zu 4 Koh- lenstoffatome enthält und deren Piperidiri- kern keine weiteren Substituenten trägt, umsetzt. PATENT CLAIM Process for the production of benzilic acid N-alkyl-piperidyl (4) esters, characterized in that benzilic acid or its functional derivatives with N-alkyl-4-o.xypiperidines, the alkyl group of which has up to 4 carbon atoms contains and whose Piperidiri- kern carries no further substituents, converts.
CH331057D1954-11-251954-11-25 Process for the preparation of basic benzilic acid estersCH331057A (en)

Applications Claiming Priority (1)

Application NumberPriority DateFiling DateTitle
CH331057T1954-11-25

Publications (1)

Publication NumberPublication Date
CH331057Atrue CH331057A (en)1958-06-30

Family

ID=4501925

Family Applications (1)

Application NumberTitlePriority DateFiling Date
CH331057DCH331057A (en)1954-11-251954-11-25 Process for the preparation of basic benzilic acid esters

Country Status (1)

CountryLink
CH (1)CH331057A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication numberPriority datePublication dateAssigneeTitle
US4697703A (en)*1986-07-021987-10-06Malcolm WillJoint prosthesis package

Cited By (1)

* Cited by examiner, † Cited by third party
Publication numberPriority datePublication dateAssigneeTitle
US4697703A (en)*1986-07-021987-10-06Malcolm WillJoint prosthesis package

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