SUBSTITUTED PHENYLALKANOL DERIVATIVES

• Main Authors: WILD A,DT, HOVY J,DT, KRAMER J,DT, DAHM J,DT, BORCK J,DT
• Format: Patent
• Language: English
• Published: 06.11.1973
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

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 R1 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, R2 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, R3 is a hydrogen atom or methyl group, R4 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 R1 is a hydroxyl group, R2 is a hydrogen atom and R3 is a methyl group, by catalytic hydrogenation of the corresponding 2-phenyl-allyl alcohol; (b) when R1 is a C 1-6 alkoxy group and R2 is a C 1-6 alkyl group, by reaction of the corresponding compound in which R1 is a hydroxyl group and R2 is a hydrogen atom with a C 1-6 alkyl iodide or bromide or a di-C 1-6 alkyl sulphate, (c) when R1 is a C 1-18 acyloxy group and R2 is a C 1-18 acyl group, by acylation of the corresponding compound in which R1 is a hydroxyl group and R2 is a hydrogen atom; (d) when R1 is a hydroxyl group and R2 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 R1 is a hydroxyl group and R2 is a hydrogen atom, by alkaline hydrolysis of the corresponding compound in which R1 is a bromine atom; (f) when R1 is a hydroxyl group and R2 is a hydrogen atom, by reaction of an appropriate 4-hydroxy-alkylaniline with an #,#1-dibromoalkanol; (g) when R1 is a hydroxyl group, R2 is a hydrogen atom and R4 is a chlorine atom, by diazotization of the corresponding compound in which R4 is an amino group, followed by treatment with cuprous chloride in hydrochloric acid; (h) when R1 is a hydroxyl group and R2 is a hydrogen atom, by alkaline hydrolysis of the corresponding 4-(3-bromo-pyrrolidino or -piperidino)-phenylalkanol; and (i) when R1 is a C 1-18 acyloxy group and R2 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.