Patent GB-886550-A (GB)
Title: Novel substituted piperidines and pyrrolidines and process for preparing same
IPC: C07D207/06
Filed: 1958-08-15
Abstract: The invention comprises compounds of the general formula <FORM:0886550/IV (b)/1> and acid addition salts thereof, wherein n is 0 or 1; R is a hydrogen atom, a methyl or methoxy group; R1 and R2 are each either hydrogen atoms or C1-3 alkyl groups; and R3, R4 and R5 are each either hydrogen atoms, hydroxy, alkoxy, alkylenedioxy or alkanoyloxy radicals having 1-4 carbon atoms, not more than two of R3, R4 and R5 being hydrogen and the preparation thereof by (a) reacting a b -phenylethylamine of the formula <FORM:0886550/IV (b)/2> with a substituted alkane of the formula <FORM:0886550/IV (b)/3> wherein X is a reactive functional group, such as a halogen atom, a carboxyl, esterified carboxyl, aldehyde or keto group, and if necessary reducing the condensation product; (b) aralkylating a compound of the general formula <FORM:0886550/IV (b)/4> with an appropriate phenethyl halide or with an appropriate phenacyl halide or anhydride and reducing the resulting product. The reductive condensations employ, in general, alkoxy or aralkoxy substituted phenethylamines and the corresponding free hydroxy substituted products are prepared by demethylation with hydrobronice acid, or debenzylation by hydrogenation.  Free hydroxyl groups may also be acylated.  The compounds of the invention may also be prepared by reacting a piperidine of the formula <FORM:0886550/IV (b)/5> with a Grignard reagent <FORM:0886550/IV (b)/6> wherein Y is a halogen atom, dehydrating the resulting alcohol and hydrogenating the double bond formed.  Alternatively, 1-homoveratryl-2-methyl-4-phenylpiperidone-6 may be reacted with methyl magnesium iodide, the complex decomposed to form 1-homoveratryl-2,6-dimethyl-4-phenyltetrahydropyridine hydrochloride and this hydrogenated.  The compounds of the invention may form two diastereoisomeric pairs which may be separated in turn into optical isomers.  b -Phenyl-d -ketoenanthic acid is prepared by reacting 1-phenylpent-1-en-3-one with mono-sodium dimethylmalonate to 1,1-dicarbomethoxy-2-phenylhexane-4-one which is hydrolysed to the free acid and decarboxylated by heating.  b -(o-Anisyl)-d -ketocaproic acid is prepared by reacting o-methoxybenzalacetone with dimethylmalonate to form dimethyl a -carboxy-b -(o-anisyl-g -acetobutyrate which is hydrolysed to a -(o-anisyl)-acetonylmalonic acid and the latter decarboxylated. b -(o-Tolyl-d -ketocaproic acid is similarly prepared.ALSO:Pharmaceutical compositions useful as neuro-sedatives and having hypotensive and antiemetic activity contain compounds of the general formula <FORM:0886550/VI/1> or their acid addition salts such as the hhdrochlorides, hydrobromides, sulphates, phosphates, maleates, benzoates, succinates or tartrates, wherein R is a hydrogen atom or a methyl or a methoxy group, R1 and R2 are either a hydrogen atom or a C1-3 alkyl group and R3, R4 and R5 are hydrogen atoms, hydroxy groups, or alkoxy, alkylenedioxy or alkanoyloxy radicals having 1-4 carbon atoms, not more than two or R3, R4 and R5 being hydrogen atoms.  The compositions may be in the form of tablets, capsules, solutions or elixirs.