Fischer esterification of 2,2,5,5-tetramethylhexanedioic acid (I) provided diethyl ester (II), which was subjected to acyloin condensation with sodium in xylene to furnish the alpha-hydroxy cyclohexanone (III). Further oxidation of (III) with CrO3 gave diketone (IV). This was condensed with 2,3-diaminopropionic acid (V) to afford, after esterification with MeOH and H2SO4, the quinoxaline ester (VI). Reduction of (VI) to alcohol (VII) employing diisobutylaluminum hydride, followed by Swern oxidation gave rise to aldehyde (VIII). Optionally, addition of vinylmagnesium bromide to (VIII), and further Swern oxidation of the allylic alcohol (IX) provided the alpha,beta-unsaturated ketone (X). Conversion to the required diketo precursor (XII) was achieved by two related strategies. Coupling of ethyl 4-formylbenzoate (XI) with the unsaturated ketone (X) using 3-benzyl-5-(2-hydroxyethyl)-4-ethylthiazolium chloride as the catalyst gave the 1,4-diketone (XII). Alternatively, addition of vinylmagnesium bromide to ethyl 4-formylbenzoate (XI) followed by oxidation with pyridinium dichromate gave unsaturated ketone (XIII). This was then coupled with quinoxaline aldehyde (VIII) in the presence of a thiazolium salt to furnish diketone (XII).
Cyclization of diketone (XII) with ammonium acetate afforded the pyrrole derivative (XIV). The methyl ester group was finally hydrolyzed with NaOH to the target carboxylic acid.