Antimalarial inter 3-meta-chloro-anilino-acrylic acid ethyl ester - prepd. by reaction of meta-chloro-aniline with 3-hydroxy-acrylic acid ethyl ester sodium salt in aq. alcoholic solvent

摘要

3-(m-Chloroanilino)acrylic acid ethyl ester (I) is new. (I) is an intermediate for 4-hydroxy-7-chloroquinoline, which in turn is a precursor of antimalarials of the chloroquine type. (I) is prepd. by reaction of m-chloroaniline with sodium 3-hydroxy-acrylic acid ethyl ester in a water/alcohol solvent mixt. in the presence of a mineral acid or acetic acid. Pref. alcohols for use as solvents are 1-4C alcohols, esp. MeOH or EtOH, or ether alcohols such as methyl glycol. The ratio of alcohol to water at the end of the reaction is pref. 10:1 to 1:5, esp. 5:1 to 1:2 v/v. Reaction temp. is pref. minus 25 to plus 25 deg.C.; the trans-isomer of (I) is formed preferentially when the reaction temp. is minus 25 to plus 25 deg.C., esp. minus 10 to plus 10 deg.C.