GB815808A - 4-phenyl isonipecotate compounds and their preparation - Google Patents

Abstract

The invention comprises compounds of the formula <FORM:0815808/IV (b)/1> (wherein R is hydroxy, alkoxy, chloro, iodo, bromo, nitro, amino or acylamino and R1 is an alkyl radical of 1 to 5 carbon atoms), their acid-addition salts and their preparation by reacting a b -(o-substituted phenyl)-ethyl halide with the appropriate isonipecotate, preferably in the form of an acid-addition salt such as a carbonate or hydrochloride, the acylamino compounds being prepared by acylation e.g. with an acid halide or anhydride, of the amino compounds prepared by this method. Preferably the reactants are heated together in an inert solvent such as a lower alcohol, advantageously in the presence of an alkali-metal bicarbonate. In examples: (1) BETA-(o-aminophenyl)-ethyl bromide hydrochloride and ethyl 4-phenyl-isonipecotate carbonate are refluxed in alcohol containing sodium bicarbonate to give, on working up, ethyl 1-(2-aminophenylethyl)-4-phenyl isonipecotate dihydrochloride; (2) the product of (1) is converted to the free base and this is acylated with acetic anhydride in acetic acid to give, on working up, ethyl 1-(2-acetylaminophenylethyl)-4-phenyl isonipecotate hydrochloride; (3) (b -(o-hydroxyphenyl)-ethyl bromide is converted by the method of (1) to ethyl 1-(2-hydroxyphenylethyl) - 4 - phenyl isonipecotate and its hydrochloride; (4) ethyl 1-(2-methoxyphenylethyl) - 4 - phenyl isonipecotate and its hydrochloride are prepared as in (3); (5) ethyl 1 - (2 - chlorophenylethyl) - 4 - phenyl isonipecotate and its hydrochloride are prepared as in (3); and (6) ethyl 1-(2-nitrophenyl ethyl)-4-phenyl isonipecotate and its hydrochloride are prepared as in (3). Reference is also made to the preparation of other compounds according to the invention wherein R is an acylamino group derived from formic, propionic, butyric, valeric, hexanoic, heptanoic, octanoic, cyclopentanecarboxylic, cyclopentylpropionic, benzoic, toluic and oxalic acids and R1 is methyl, propyl or amyl. Starting materials. b -(o - aminophenyl)-ethyl bromide hydrochloride is prepared by reduction of b -(o-nitrophenyl)-ethyl bromide with stannous chloride and hydrochloric acid and is converted to b -(o-hydroxyphenyl)-ethyl bromide by heating with sulphoric acid and sodium nitrite.