Patent EP-0147850-A2 (EP)
Inventor: GRELL WOLFGANG
IPC: A61K31/395
Filed: 1984-12-27
Abstract: 1. Claims for the contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE Phenylacetic acid derivatives of general formula  see diagramm : EP0147850,P23,F1  wherein R1 represents a pyrrolidino, piperidino, hexamethyleneimino, methyl-pyrrolidino, dimethyl-pyrrolidino, 2-methyl-piperidino, 3-methyl-piperidino, 4-methyl-piperidino, 3,3-dimethyl-piperidino, cis-3,5-dimethyl-piperidino or trans-3,5-dimethyl-piperidino group, R2 represents a hydrogen or halogen atom or a methyl or methoxy group, R3 represents a hydrogen atom, an alkyl group with 1 to 4 carbon atoms, an n-pentyl or 3-methyl-n-butyl group or a phenyl group optionally substituted by a halogen atom or by a methyl or methoxy group, R4 represents a hydrogen atom, a methyl, ethyl or allyl group and W represents a methyl, hydroxymethyl, formyl, carboxy or alkoxycarbonyl group with a total of 2 to 5 carbon atoms, whilst the alkyl part of the alkoxy group may be substituted by a phenyl group, the enantiomers and salts thereof. 1. Claims for the contracting State : AT Process for preparing new phenylacetic acid derivatives of general formula  see diagramm : EP0147850,P25,F4  wherein R1 represents a pyrrolidino, piperidino, hexamethyleneimino, methyl-pyrrolidino, dimethyl-pyrrolidino, 2-methyl-piperidino, 3-methyl-piperidino, 4-methyl-piperidino, 3,3-dimethyl-piperidino, cis-3,5-dimethyl-piperidino or trans-3,5-dimethyl-piperidino group, R2 represents a hydrogen or halogen atom or a methyl or methoxy group, R3 represents a hydrogen atom, an alkyl group with 1 to 4 carbon atoms, an n-pentyl or 3-methyl-n-butyl group or a phenyl group optionally substituted by a halogen atom or by a methyl or methoxy group, R4 represents a hydrogen atom, a methyl, ethyl or allyl group and W represents a methyl, hydroxymethyl, formyl, carboxy or alkoxycarbonyl group with a total of 2 to 5 carbon atoms, whilst the alkyl part of the alkoxy group may be substituted by a phenyl group, the enantiomers and salts thereof, characterised in that a) an amine of general formula  see diagramm : EP0147850,P25,F1  wherein R1 to R3 are defined as hereinbefore is acylated with a carboxylic acid of general formula  see diagramm : EP0147850,P25,F2  wherein R4 is defined as hereinbefore and W' has the meanings given for W hereinbefore or represents a carboxy group protected by a protecting group, or with the reactive derivatives thereof, which may optionally be prepared in the reaction mixture, and if necessary any protecting group used is split off, or b) in order to prepare a compound of general formula I wherein W represents a carboxy group, a group A in a compound of general formula  see diagramm : EP0147850,P25,F3 wherein R1 to R4 are defined as hereinbefore and A represents a group which may be converted into a carboxy group by hydrolysis, thermolysis or hydrogenolysis, is converted into a carboxy group, c) in order to prepare a compound of general formula I wherein R4 represents a hydrogen atom or a methyl or ethyl group, a compound of general formula  see diagramm : EP0147850,P26,F1  wherein R1 to R3 are defined as hereinbefore is reacted with a compound of general formula  see diagramm : EP0147850,P26,F3  wherein R4 and W are defined as hereinbefore, or d) in order to prepare compounds of general formula I wherein R4 represents a hydrogen atom, a protecting group is cleaved from a compound of general formula  see diagramm : EP0147850,P26,F6  wherein R1 to R3 are defined as hereinbefore, W' has the meanings given for W hereinbefore or represents a group which can be converted into a carboxy group and R5 represents a protecting group for a hydroxy group or e) in order to prepare compounds of general formula I wherein R4 represents a methyl, ethyl or allyl group, a compound of general formula  see diagramm : EP0147850,P26,F7 wherein R1 to R3 and W are defined as hereinbefore, is reacted with a compound of general formula R'4 -X wherein R'4 has the meanings given for R4 hereinbefore, with the exception of the hydrogen atom, and X represents a nucleophilically exchangeable group or, together with the adjacent hydrogen atom, represents a diazo group if R'4 represents a methyl or ethyl group, and subsequently, if necessary, a compound thus obtained is hydrolysed, or f) a compound of general formula  see diagramm : EP0147850,P26,F2  wherein R1 , R2 , R4 and W are defined as hereinbefore and Y represents a group of formula  see diagramm : EP0147850,P26,F4  or  see diagramm : EP0147850,P26,F5 wherein R3 is defined as hereinbefore and R6 and R7 together with the carbon atom between them represent an alkylidene group with 1 to 4 carbon atoms, is reduced and subsequently, if desired, a compound of general formula I thus obtained wherein R2 represents a halogen atom and/or R3 represents a halophenyl group and/or W represents a hydroxymethyl group which has been converted into a halomethyl group, is converted by dehalogenation into a corresponding compound of general formula I wherein R2 represents a hydrogen atom and/or R3 represents a phenyl group and/or W represents a methyl group, and/or a compound of general formula I thus obtained wherein W represents the carboxy group is converted by esterification into a corresponding compound of general formula I wherein W represents an alkoxycarbonyl or phenylalkoxycarbonyl group, and/or a compound of general formula I thus obtained wherein W represents a carboxy, alkoxycarbonyl or phenylalkoxycarbonyl group is converted by reduction into a corresponding compound of general formula I wherein W represents a formyl or hydroxymethyl group, and/or a compound of general formula I thus obtained wherein W represents a hydroxymethyl group is converted by oxidation into a corresponding compound of general formula I wherein W represents a formyl or carboxy group, and/or a compound of general formula I thus obtained wherein W represents a carboxy group is converted by conversion into a sulphonic acid hydrazide and subsequent disproportionation into a corresponding compound of general formula I wherein W represents a formyl group, and/or a racemic compound of general formula I thus obtained wherein R3 has the meanings given hereinbefore, with the exception of the hydrogen atom, is resolved by chromatography on chiral phases into the enantiomers thereof, and/or a compound of general formula I thus obtained is converted into the salts thereof, more particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases.