Patent GB-1359600-A (GB)
Title: Substituted phenyl-alkanol derivatives their preparation and compo sitions containing them
IPC: C07D491/10
Filed: 1972-03-10
Abstract: 1359600 4 - (3 - Hydroxy - pyrrolidino or -piperidino)-phenylalkanol derivatives MERCK PATENT GmbH 10 March 1972 [25 March 1971] 11292/72 Heading C2C Novel 4 - (3 - hydroxy - pyrrolidino or -piperidino)-phenylalkanol derivatives of the general formula wherein R<SP>1</SP> is a hydroxyl, C 1-6  alkoxy, C 3-6  cycloalkoxy, C 6-12  aryloxy, C 7-12  aralkoxy or C 1-18  acyloxy group, or a heterocycloalkoxy group with up to 6 carbon atoms which may optionally be substituted with an alkoxy group, R<SP>2</SP> is a hydrogen atom or a C 1-6  alkyl, C 3-6  cycloalkyl, C 6-12  aryl, C 7-12  aralkyl or C 1-18  acyl group, R<SP>3</SP> is a hydrogen atom or methyl group, R<SP>4</SP> is a chlorine or bromine atom or a methyl group and n is 2 or 3, and acid addition and quaternary ammonium salts thereof are prepared, e.g. (a) when R<SP>1</SP> is a hydroxyl group, R<SP>2</SP> is a hydrogen atom and R<SP>3</SP> is a methyl group, by catalytic hydrogenation of the corresponding 2-phenyl-allyl alcohol; (b) when R<SP>1</SP> is a C 1-6  alkoxy group and R<SP>2</SP> is a C 1-6  alkyl group, by reaction of the corresponding compound in which R<SP>1</SP> is a hydroxyl group and R<SP>2</SP> is a hydrogen atom with a C 1-6  alkyl iodide or bromide or a di-C 1-6  alkyl sulphate, (c) when R<SP>1</SP> is a C 1-18  acyloxy group and R<SP>2</SP> is a C 1-18  acyl group, by acylation of the corresponding compound in which R<SP>1</SP> is a hydroxyl group and R<SP>2</SP> is a hydrogen atom; (d) when R<SP>1</SP> is a hydroxyl group and R<SP>2</SP> is a hydrogen atom, by reduction of an appropriate phenylalkanal, phenylalkanoic acid or ester thereof or 4-(3-oxo-pyrrolidino or -piperidino)-phenylalkanol with lithium aluminium hydride; (e) when R<SP>1</SP> is a hydroxyl group and R<SP>2</SP> is a hydrogen atom, by alkaline hydrolysis of the corresponding compound in which R<SP>1</SP> is a bromine atom; (f) when R<SP>1</SP> is a hydroxyl group and R<SP>2</SP> is a hydrogen atom, by reaction of an appropriate 4-hydroxy-alkylaniline with an #,#<SP>1</SP>-dibromoalkanol; (g) when R<SP>1</SP> is a hydroxyl group, R<SP>2</SP> is a hydrogen atom and R<SP>4</SP> is a chlorine atom, by diazotization of the corresponding compound in which R<SP>4</SP> is an amino group, followed by treatment with cuprous chloride in hydrochloric acid; (h) when R<SP>1</SP> is a hydroxyl group and R<SP>2</SP> is a hydrogen atom, by alkaline hydrolysis of the corresponding 4-(3-bromo-pyrrolidino or -piperidino)-phenylalkanol; and (i) when R<SP>1</SP> is a C 1-18  acyloxy group and R<SP>2</SP> is a C 1-18  acyl group, by catalytic hydrogenation of the corresponding compound in which the heterooyclic ring contains a C-C double bond; followed optionally by salification or desalification of the product or separation of a resulting racemate into its optical antipodes. Pharmaceutical compositions having antiinflammatory activity comprise, as active ingredient, a 4-(3-hydroxy-pyrrolidino or -piperidino)-phenylalkanol derivative of the general formula above or an acid addition or quaternary ammonium salt thereof, together with an inert, physiologically acceptable carrier therefor, and may be administered parenterally, enterally or locally.