Preparation of substituted alkenoic acids

A process for the preparation of a compound of Formula E-I ##STR40## wherein n is 2, 3, 4 or 5;

• L is ortho-, meta- or para-phenylene;
• each R.sup.a is hydrogen or the two together form a double bond;
• and
• R is (3-12C)alkyl, (3-12C)alkenyl, (3-12C)alkynyl, 2-phenylcyclopropyl or R.sup.b -(1-6C)alkyl in which R.sup.b is (3-8C)cycloalkyl, phenyl, tetrahydropyranyl, morpholino, piperidino or pyrrolidino wherein a phenyl group of the radical R may bear a 4-substituent selected from halo, (1-2C)alkyl and (1-2C)alkoxy;
• a cyclohexyl group of the radical R may bear a 4-substituent selected from (1-2C)alkyl and (1-2C)alkoxy;
• and in which one or two methylene groups of a (3-12C)alkyl, (3-12C)alkenyl, (3-12C)alkynyl, or the alkyl portion of R.sup.b -(1-6C)alkyl may be replaced by an oxy group;
• and further provided that at least two carbon atoms separate any oxygens or nitrogens in the residue --NHR;
• or a pharmaceutically acceptable salt thereof, which comprises
• (i) cross coupling a compound of Formula VIII ##STR41## with a compound of Formula IX ##STR42## in the presence of a catalyst Q wherein the cross coupling reaction is the Stille reaction;
• one of Y and Z is bromo, iodo, or trifluoromethylsulfonyloxy (TfO);
• the other of Y and Z is SnR.sup.t 3, wherein R.sup.t is lower alkyl;
• and Q is a Stille catalyst;
• and
• --COOR.sup.p represents a carboxy group in a protected form stable to the cross coupling conditions
• to afford a compound of Formula E-II, ##STR43## and (ii) converting the protected carboxy group --COOR.sup.p into the carboxy group --COOH;
• and
• whereafter, when a pharmaceutically acceptable salt of a compound of Formula E-I is required, it is obtained by reacting the acid of Formula E-I with a physiologically acceptable base or by reacting a basic compound of Formula E-I with a physiologically acceptable acid or by any other conventional procedure.