CH409940A - Procédé de préparation d'un nouveau dérivé de l'adamantane - Google Patents

Description

  

  
 



  Process for preparing a new derivative of adamantane
 The present invention relates to a process for preparing a new derivative of adamantane of formula (I):
EMI1.1
 (either, in short: Ad-O-CH2-CH-COOH) or (adamantyl-1 'oxy) -3 propionic acid, in the free state or salified'.



   According to the process of the invention, 1 hydroxy-1 adamantane of formula is converted:
 Ad-OH (II) in (benzyloxy-2 'ethoxy) -l adamantane of formula (IJI):
EMI1.2

 The compound (III) is then hydrogenolysed to (adamantyl-1 'oxy) -2 ethanol of formula (IV):
   Ad-O-CH2-CH20H (IV) and this alcohol is esterified with paratoluene-sulfonyl chloride to give compound (V):
EMI1.3

 Under the action of an alkaline cyanide, the compound (V) gives the nitrile (VI)
   ACL-O-CH, -CH, -CN (VI) whose hydrolysis leads to the desired acid (I).



   The salts of the acid (I), especially the salts formed with the alkali metals, the alkaline earth metals, and certain salts of amines such as the salts of ethanolamine, are also rutile. These salts can be prepared by neutralization of the acid (I) or, particularly for the alkaline salts, directly by alkaline hydrolysis of (adamantyl-oxy) -3 propionitrile (VI).



   (Adamantyl-1 'oxy) -3 propionic acid and its salts exhibit interesting pharmacological properties; in particular, they are very active choleretics.



   The following examples illustrate the process of the invention:
 Example 1
 The paratoluenesulfonyloxy-1 benzyloxy-2 ethane is condensed on sodium hydroxy-1 adamantane, in boiling xylene, and obtained (with a yield of 81 / o) the (benzyloxy-2 'ethoxy) -1 adamantane (PE1 = 190-1950) which is then debenzylated (with a yield of 750/0) by hydrogenation in the presence of palladium in acetic acid for 7 hours at 850 C under a pressure of 50 kg / cm2 of hydrogen.



  Under these conditions, partially acetylated i '(adamantyl-1' oxy) -2 ethanol is obtained, which is saponified with alcoholic sodium hydroxide to completely free the alcohol.



   A solution of 35 g of (adamantyl-l 'oxy) -2 ethanol in 150 cm9 of anhydrous pyridine, previously cooled to 00 C, is mixed with a solution, also cooled, of 34 g of paratoluenesulfonyl chloride in 300 cm3 of pyridine anhydrous.



   It is left for 20 hours at 40 C, then poured onto 1.8 kg of crushed ice. I1 immediately forms a white precipitate which is filtered off after melting the ice. Washed with 7 times 30 cm8 of ice-cold water and dried under reduced pressure.



   44.5 g of paratoluene sulfonyloxyethoxy-1 adamantane are obtained, melting at 1140 ° C., which can be recrystallized from methanol with a yield of 90%. The product obtained then melts at 1150 C.



   58 g of p.toluenesulfonyloxyethoxy-1 adamantane, prepared as above, are dissolved in 650 cm2 of absolute ethanol, while lukewarming. A solution of 22 g of potassium cyanide in 150 cm3 of water is added and the mixture is boiled under reflux for 7 hours. The ethanol is evaporated off in a water bath under reduced pressure and the residue is taken up in 100 cm3 of water. Extracted with 500con3 then 4 times 100 cm2 of ether. The ethereal extracts are washed with 2 times 50 cm3 of water and dried over sodium sulfate.

   After evaporation of the solvent, a crystalline mass of 33 g of (adamantyl 1 'oxy) -3 propionitrile, melting at around 450 ° C., which can be purified by rectification (PE05 = 125-1300 ° C.) is obtained.



   A solution of 20 g of (adamantyl-oxy) -3 propionitrile (PEo, 3 = 125-1300 C) in 250 cm3 of an alcoholic potassium hydroxide solution (150 g of potassium in 50 g) is boiled for 5 hours. cm3 of water and sufficient quantity of absolute ethanol to make 250 cl0).



  The alcohol is then evaporated off in a water bath under reduced pressure, the colorless residue is taken up in 100 cm2 of water, the aqueous phase washed with 4 times 50 cm3 of ether and acidified.



   The colorless precipitate formed is filtered off. This consists of 2.3 g of pure (adamantyi-l 'oxy) -3 propionic acid, melting at 650 C.



   Example 2
 A solution of 2 g of (adamantyl-l 'oxy) -3 propionitrile (prepared according to Example 1) in 30 cl 2 of methanol with 6.3 g of barite suspended in 30 cl 2 of methanol is boiled under reflux for 4.30 h. 12 cl2 of water.



   After cooling, 2 cm3 of concentrated sulfuric acid are added, the precipitate is filtered off and washed with 4 times 20 cm3 of methanol and with 20 cm3 of ether. All the above filtrates are combined, basified clearly with concentrated sodium hydroxide and concentrated to mid-volume. The residual solution is cooled, washed with 3 times 100 cm3 of ether, acidified with concentrated hydrochloric acid and the acid released is extracted with 3 times 100 cm3 of ether. The ethereal solution is washed with 10 cm3 of water, dried over sodium sulfate, filtered and evaporated. The oily residue is dissolved in 40 cm3 of 0.25 N sodium hydroxide by heating at 50 ° C., decolorizing black is added hot, filtered, cooled and acidified with 4 N hydrochloric acid.

   The colorless precipitate formed is filtered off, washed with 3 times 2 cm3 of water and dried.



   0.63 g of (adamantyl-oxy) 3 propionic acid is obtained, melting at 650 C.
  

 

Claims (1)

CLAIM Process for preparing (adamantyl-l 'oxy) -3 propionic acid of formula EMI2.1 in the free state or in the form of a salt, characterized in that hydroxy-l adamantane is converted into benzyioxy-2 'ethoxy) -l adamantane, in that the latter is hy drogenolysis to (adamantyl-l 'oxy) -2 ethanol, in that the latter is esterified with p-toluenesulfonyl chloride, in that the ester is converted into (adamantyl-oxy) -3 propionitrile by reaction with a cyanide alkaline and in that said nitrile is hydrolyzed. SUB-CLAIM Process according to claim, characterized in that (adamantyl-l 'oxy) -3 propionic acid is obtained in the free state and in that it is converted into a salt by neutralization using the appropriate base.