GB1012008A - Process for the production of pyrrolidine compounds - Google Patents

Abstract

Substituted pyrrolidines of general formula <FORM:1012008/C2/1> where R represents hydrogen, or an alkyl or alkanoyl group having 1-4 carbon atoms, and R1 represents an alkyl group having 2-4 carbon atoms, are prepared by reacting a dinitrile compound of formula <FORM:1012008/C2/2> with hydrogen and methanol at a temperature of 140-190 DEG C. and a pressure of at least 100 atms. in the presence of a Raney nickel or Raney cobalt catalyst, and, if desired, the product is converted to an acid addition salt thereof. The preferred quantity of catalyst employed is approximately 25% by weight of the dinitrile starting material. The free bases and acid addition salts of the invention exist in racemic as well as d- and loptically active forms. The separated isomers may be obtained by forming salts with optically active acids, followed by fractional crystallization and regeneration of the d- and lfree base forms. The m - substituted a - phenyl - a - alkyl-succinonitrile starting materials in which R represents hydrogen or a lower alkyl group can be prepared by heating the appropriate m-substituted phenyl alkyl ketone at reflux temperature with ethyl cyanoacetate, acetic acid and b -alanine in benzene, with continuous removal of the water formed, and heating the resultant m-substituted ethyl a -cyano-b -alkyl-cinnamate at reflux temperature with potassium cyanide or sodium cyanide in aqueous ethanol. The m-alkoxyphenyl alkyl ketones are obtained by reacting the corresponding m-hydroxy compounds with a dialkyl sulphate in aqueous-alcoholic sodium hydroxide, or by reaction with an alkyl halide. The m-substituted a -phenyl-a -succinonitriles in which R represents a lower alkanoyl group can be prepared by reaction of the corresponding phenol with an alkanoic acid halide or anhydride. Specification 1,002,851 is referred to.ALSO:Therapeutic compositions useful as analgesics and which may be administered orally or parenterally as tablets, pills, sachets, and powders, or as solutions or suspensions for oral use or sterile injectable solutions or suspensions in ampoules contain as active ingredient compounds of formula <FORM:1012008/A5-A6/1> in which R represents hydrogen or an alkyl or alkanoyl group having 1-4 carbon atoms, and R1 represents an alkyl radical having 2-4 carbon atoms, or acid addition salts thereof. Specification 1,002,851 is referred to.