GB1032872A - Aryloxy acetic acid amides and processes for their production - Google Patents

Abstract

Novel compounds of formula <FORM:1032872/C2/1> where X represents -CH2CH2- or -CH = CH-, and R1, R2, R3 and R4 represent alkyl groups having 1-5 carbon atoms, or R3 and R4 together with the nitrogen, optionally with an oxygen atom as ring member, represent a saturated heterocyclic radical having 5-7 ring members, are prepared (1) by reacting a compound of Formula II <FORM:1032872/C2/2> or a salt thereof with a reactive ester of a hydroxyl compound of formula HO-CH2-CO-NR3R4 in the presence of an acid binding agent, (2) by esterifying an acid of Formula I in which R1 is hydrogen or a reactive functional derivative thereof, (3) by reacting an aryloxy-acetic acid of Formula II in which -OH is replaced by -OCH2COOH, or a reactive functional derivative of such an acid with a compound of formula HNR3R4, (4) by heating an aryloxy-acetic acid as defined in (3) with a carbamoyl chloride of formula Cl-CO-NR3R4, (5) by transesterification of a compound of Formula I in which the alkyl group R1 has fewer carbon atoms than the desired group R1, and (6) for compounds of Formula I in which X represents -CH2CH2-, by reducing the corresponding compound in which X represents -CH = CH-. Therapeutic compositions useful as short-acting anaesthetics and which can be applied intravenously contain as active ingredient compounds of Formula I above. The 4-carbamoylmethoxy-cinnamic and -hydrocinnamic acid starting materials of process (2) may be prepared by reacting a 3-alkoxy-4-hydroxybenzaldehyde in the presence of ethanolic sodium hydroxide with a suitable chloroacetic acid amide, condensing the compounds obtained with malonic acid in pyridine and piperidine, the condensation products then being partially decarboxylated and optionally catalytically hydrogenated. The 3-alkoxy-4-(carboxymethoxy)-cinnamic and -hydrocinnamic acid ester starting materials of processes (3) and (4) may be prepared by etherifying 3-alkoxy-4-hydroxy-cinnamic and hydrocinnamic acid alkyl esters with chloroacetic acid in the presence of ethanolic sodium hydroxide. 3-Methoxy-4-hydroxy-cinnamic and-hydrocinnamic acid esters may be produced by esterification; the hydrocinnamic acid esters may also be prepared by catalytic hydrogenation of the corresponding cinnamic acid esters.