CH299535A - Process for the production of an ether of (+) - 3-oxy-N-methyl-morphinans. - Google Patents

Description

  

  Process for the production of an ether of (+) - 3-oxy-N-methyl-morphinans. It has been found that the ethers of (+) - 3-oxy-N-methyl-morphinans and their salts containing more than 1 carbon atom in the ether group are valuable antitussive agents and compared to the racemic and the (-) - compounds have the advantage that they do not have the undesirable analgesic effect of cough suppressants.



  These ethers and their salts can be obtained according to the invention by treating (+) - 3-oxy-N-methyl-morphinane with an etherifying agent suitable for introducing more than 1 carbon atom containing alkyl and alkenyl radicals and, if desired, hydrogenating the unsaturated ethers.



  A compound of the formula is preferably used as the etherifying agent
EMI0001.0023
    where R1, R2 and R3 are identical or different lower alkyl or alkenyl radicals, at least one of them - namely that of J. von Braun (Liebigs Annalen der Chemie, Volume 382, [1911], page 5) in Reaction occurring - contains at least two carbon atoms.

      The corresponding saturated alkyl ethers can be prepared from the alkenyl ethers by hydrogenation. The new ethers give water-soluble salts with inorganic or organic acids. They are said to be used as remedies.



  The subject of the patent is now a process for the production of <B> (+) </B> -3-propyloxy- N-methyl-morphinane, which is characterized in that (+) -3-oxy-N- methyl morphinan with an etherifying agent of the formula
EMI0001.0039
         where R1 and R2 are lower alkyl or alkenyl radicals and R3 is an allyl radical, treated, and the resulting (+)

  -3-Allyl-oxy-N-ynethyl-morphinan hydrogenated.



  <I> Example: </I> 48.2 parts by weight of phenyl-allyl-dimethylammonium bromide are dissolved in 50 parts by weight of iNethanol and mixed with 41 parts by weight of methyl alcoholic potassium hydroxide solution (27.7 percent) and 40 parts by volume of toluene.

   The resulting potassium bromide is filtered off with exclusion of moisture and carbon dioxide. 25.7 parts by weight of (+) - 3-oxy-N-methylmorphinane are dissolved in 800 parts by volume of toluene and, in order to render the solution anhydrous, 250 parts by volume of toluene are distilled off, cooled and the allylation liquor is then added.

   The solution is then heated with stirring, with first methanol, then a mixture of methanol and toluene, and finally toluene being distilled off. After cooling, the reaction solution is washed with ice-cold, dilute sodium hydroxide solution. The residue remaining after distilling off is distilled in a high vacuum. Boiling point 139 to 149 C / 0.006 mm. The hydrobromide crystallizes from alcohol-acetone and melts at 167-168 C; [a] D = + 32.8 (c = 3 in water).



  20.7 parts by weight of (+) - 3-allyl-oxy-N-methy 1-morphinane hydrobromide are hydrogenated in 150 parts by volume of methanol with 6 parts by weight of Pd-carbon (51 / o Pd-metal) and hydrogen.



  After the calculated amount of hydrogen has been absorbed. is separated from the catalyst and concentrated. The residue is taken up in water, made alkaline with sodium hydroxide solution, the base is taken up in ether and the ether is distilled off. The (+) -3-propyloxy-N-methyl-morphinan forms. a tartrate which melts with 2 mol of crystal water with sintering at 98-105 C; [a] 20 = +32.1.6 (c = 3 in methanol).

 

Claims (1)

PATENT CLAIM: Process for the production of (+) -3 propyloxy-N-methyl-morphinan, characterized in that (+) -3-oxy-N-methyl-morphinan with an etherifying agent of the formula EMI0002.0033 where R, and R2 are lower alkyl or alkenyl radicals and R.3 is an allyl radical, treated and hydrogenated the (+) -3-allyl-oxy-N-methyl-morphinan. The new compound forms a tartrate which melts with 2 mol of crystal water under sintering at 98-105 C; [a] D = + 32.16 (c = 3 in methanol).