GB924589A - Azetidine derivatives and process for their preparation - Google Patents

Abstract

The invention comprises azetidine-2-ones of the general formula: <FORM:0924589/IV(a)/1> wherein R1 represents a hydrocarbon radical which may be substituted in any aromatic nucleus present by halogen and/or alkoxy; R2 represents a cycloalkyl radical or an aryl or aralkyl radical optionally substituted by halogen or alkoxy; R3 represents hydrogen, a lower alkyl or alkenyl radical, or a lower dialkylaminoalkyl radical the alkyl radicals of which may be bound to each other direct or by way of oxygen; and R4 represents hydrogen or a lower alkyl group (the term 'lower' indicates that the group so described contains up to 6 carbon atoms) and the preparation thereof by cyclising a b -aminocarboxylic acid: R3NH,CR1R2,CHR4,COOH or a reactive functional derivative thereof and if desired, treating the compound obtained provided that R3 therein represents hydrogen, with a reactive ester of an alcohol R31OH where R31 represents a radical corresponding to the definition for R3 with the exception of hydrogen, in the presence of an acid binding agent. Ring closure methods are more specifically (a) treating an alkyl ester of the b -amino propionic acid with an alkyl magnesium halide and hydrolysing the metal complex formed; (b) treating the acid chloride with a tertiary organic base; (c) heating, preferably under reduced pressure, an N-alkanoyl derivative of the free acid; and (d) treating the b -aminocarboxylic acid with phosphorus trichloride or with an N,N1-disubstituted carbodiimide. The b -amino propionic acids used as starting materials are prepared by Hofmann degradation of the a ,a -disubstituted-succin-a -amide acid. b -(p-Chlorophenyl)-b - ethyl-b -aminopropionic acid chloride hydrochloride is prepared from the acid and thionyl chloride. Central depressant, soporific and sedative compositions comprise the azetidine-2-ones of the invention in the form of tablets, coated tablets or capsules for peroral administration.