CH375712A

CH375712A - Process for the preparation of new, hydroxylated indole derivatives

Info

Publication number: CH375712A
Application number: CH6842559A
Authority: CH
Inventors: Albert Dr Hofmann; Franz Dr Troxler
Original assignee: Sandoz Ag
Priority date: 1959-01-16
Filing date: 1959-01-16
Publication date: 1964-03-15

Description

  

  
 



  Verfahren zur Herstellung von neuen, hydroxylierten Indol-Derivaten
Es wurde gefunden, dass man zu neuen, hydroxylierten Indol-Derivaten der Formel I,
EMI1.1     
 in welcher   R1    und R2 für Methyl- oder   Äthylgruppen    stehen, gelangen kann, indem man 6-Benzyloxy-indol der Formel II,
EMI1.2     
 mit Oxalylchlorid und dann mit Dimethyl- oder Di äthylamin umsetzt, das Reaktionsprodukt reduziert und die Benzylgruppe abspaltet.



   Beispiel   6-Hydroxy-dimethyltryp tamin   
Man löst 6 g 6-Benzyloxy-indol in 200   cm3    Äther und lässt unter Rühren bei einer Temperatur von   0-2"    4,8 g Oxalylchlorid zutropfen. 30 Minuten nach beendetem Eintropfen gibt man unter Eiskühlung und Rühren langsam 10 g wasserfreies Dimethylamin hinzu, rührt noch einige Minuten bei Zimmertemperatur und filtriert ab. Der Niederschlag wird gut mit Wasser gewaschen und der wasserunlösliche Teil am Vakuum getrocknet und hierauf aus einem Gemisch von Benzol/Methanol unter allmählichem Petrolätherzusatz umkristallisiert. Smp.



     202-2040.   



   Eine Lösung von 4 g des erhaltenen [6-Benzyloxy-indolyl-(3)]-glyoxylsäure-dimethylamids in 80   cm3    abs. Dioxan lässt man unter energischem Rühren zu einer Lösung von 5 g LiAIH4 in 100   cm3    abs. Dioxan zutropfen und rührt das Gemisch 24 Stunden am Rückfluss bei Siedetemperatur. Nun zersetzt man den Komplex und überschüssiges Reduktionsmittel mit Methanol und gesättigter Natriumsulfat-Lösung, filtriert und schüttelt das Filtrat zwischen Weinsäure Lösung und Äther aus. Nach üblicher Freisetzung und Isolierung der Basen erhält man ein Öl, das zur Abtrennung von Nebenprodukten in benzolischer Lösung durch eine Säule von Aluminiumoxyd filtriert wird. Das so gewonnene farblose Ö1 kristallisiert aus Benzol in Prismen vom Smp.   87-880.   



   Eine Lösung von 2 g 6-Benzyloxy-dimethyltryptamin in 100   cm3    Methanol wird mit 1 g Palladium auf Aluminiumoxyd-Träger und Wasserstoff geschüttelt. Nach beendeter Wasserstoffaufnahme wird filtriert und das Filtrat zur Trockne verdampft. Den Rückstand destilliert man am Hochvakuum bei 200 bis   220O    und kristallisiert hierauf das Destillat aus Äther um. Smp.   165-166 .    Kellersche Farbreaktion: olivenbraun.  



   PATENTANSPRUCH
Verfahren zur Herstellung von neuen, bisher unbekannten 6-Hydroxy-indolderivaten der Formel I,
EMI1.3     
 in welcher   Rt    und R2 je für eine   Metbyl oder    Äthyl 

**WARNUNG** Ende DESC Feld konnte Anfang CLMS uberlappen**.



   



  
 



  Process for the preparation of new, hydroxylated indole derivatives
It has been found that new, hydroxylated indole derivatives of the formula I,
EMI1.1
 in which R1 and R2 stand for methyl or ethyl groups, can be achieved by 6-benzyloxy-indole of the formula II,
EMI1.2
 with oxalyl chloride and then with dimethyl or diethylamine, the reaction product is reduced and the benzyl group is split off.



   Example 6-Hydroxy-dimethyltrypamine
6 g of 6-benzyloxy-indole are dissolved in 200 cm3 of ether and 4.8 g of oxalyl chloride are added dropwise while stirring at a temperature of 0-2 ". 30 minutes after the drop-in is complete, 10 g of anhydrous dimethylamine are slowly added while stirring with ice, stir for a few more minutes at room temperature and filter off. The precipitate is washed thoroughly with water and the water-insoluble part is dried in vacuo and then recrystallized from a mixture of benzene / methanol with the gradual addition of petroleum ether.



     202-2040.



   A solution of 4 g of the [6-benzyloxy-indolyl- (3)] -glyoxylic acid dimethylamide obtained in 80 cm3 of abs. Dioxane is added with vigorous stirring to a solution of 5 g LiAlH4 in 100 cm3 abs. Dioxane is added dropwise and the mixture is stirred under reflux at boiling temperature for 24 hours. The complex and excess reducing agent are now decomposed with methanol and saturated sodium sulphate solution, filtered and the filtrate is shaken out between tartaric acid solution and ether. After the bases have been liberated and isolated in the usual way, an oil is obtained which is filtered through a column of aluminum oxide in a benzene solution to separate by-products. The colorless oil obtained in this way crystallizes from benzene in prisms with a melting point of 87-880.



   A solution of 2 g of 6-benzyloxy-dimethyltryptamine in 100 cm3 of methanol is shaken with 1 g of palladium on an aluminum oxide carrier and hydrogen. After the hydrogen uptake has ended, it is filtered and the filtrate is evaporated to dryness. The residue is distilled in a high vacuum at 200 to 220 ° and the distillate is then recrystallized from ether. M.p. 165-166. Keller's color reaction: olive brown.



   PATENT CLAIM
Process for the preparation of new, previously unknown 6-hydroxy-indole derivatives of the formula I,
EMI1.3
 in which Rt and R2 each represent a methyl or ethyl

** WARNING ** End of DESC field could overlap beginning of CLMS **.

Claims

** WARNING ** Beginning of CLMS field could overlap end of DESC **.

Process for the preparation of new, hydroxylated indole derivatives It has been found that new, hydroxylated indole derivatives of the formula I, EMI1.1 in which R1 and R2 stand for methyl or ethyl groups, can be achieved by 6-benzyloxy-indole of the formula II, EMI1.2 with oxalyl chloride and then with dimethyl or diethylamine, the reaction product is reduced and the benzyl group is split off.

Example 6-Hydroxy-dimethyltrypamine 6 g of 6-benzyloxy-indole are dissolved in 200 cm3 of ether and 4.8 g of oxalyl chloride are added dropwise while stirring at a temperature of 0-2 ". 30 minutes after the drop-in is complete, 10 g of anhydrous dimethylamine are slowly added while stirring with ice, stir for a few more minutes at room temperature and filter off. The precipitate is washed thoroughly with water and the water-insoluble part is dried in vacuo and then recrystallized from a mixture of benzene / methanol with the gradual addition of petroleum ether.

202-2040.

A solution of 4 g of the [6-benzyloxy-indolyl- (3)] -glyoxylic acid dimethylamide obtained in 80 cm3 of abs. Dioxane is added with vigorous stirring to a solution of 5 g LiAlH4 in 100 cm3 abs. Dioxane is added dropwise and the mixture is stirred under reflux at boiling temperature for 24 hours. The complex and excess reducing agent are now decomposed with methanol and saturated sodium sulphate solution, filtered and the filtrate is shaken out between tartaric acid solution and ether. After the bases have been liberated and isolated in the usual way, an oil is obtained which is filtered through a column of aluminum oxide in a benzene solution to separate by-products. The colorless oil obtained in this way crystallizes from benzene in prisms with a melting point of 87-880.

A solution of 2 g of 6-benzyloxy-dimethyltryptamine in 100 cm3 of methanol is shaken with 1 g of palladium on an aluminum oxide carrier and hydrogen. After the hydrogen uptake has ended, it is filtered and the filtrate is evaporated to dryness. The residue is distilled in a high vacuum at 200 to 220 ° and the distillate is then recrystallized from ether. M.p. 165-166. Keller's color reaction: olive brown.

PATENT CLAIM Process for the preparation of new, previously unknown 6-hydroxy-indole derivatives of the formula I, EMI1.3 in which Rt and R2 each stand for a methyl or ethyl group, characterized in that 6 benzyloxy-indole of the formula II EMI2.1 with oxalyl chloride and then with dimethyl or diethylamine, the reaction product is reduced and the benzyl group is split off.