合成路线1

The reaction of 2-fluoro-5-(trifluoromethyl)phenol (I) with allyl bromide (II) by means of K2CO3 in DMF gives the phenol ether (III), which is submitted to an allylic rearrangement by heating at 190 C to yield 2-allyl-6-fluoro-3-(trifluoromethyl)phenol (IV). The cyclization of (IV) by means of MCPBA and KOH affords the dihydrobenzofuran (V), which is treated with Ac2O and pyridine to provide the acetate (VI). The dehydrogenation of (VI) by means of NBS and AIBN, followed by a treatment with tBu-OK and K2CO3 in methanol, gives 1-[7-fluoro-4-(trifluoromethyl)benzofuran-2-yl]methanol (VII), which is oxidized with oxalyl chloride and TEA in DMSO to yield the corresponding carbaldehyde (VIII). The condensation of (VIII) with 4-acryloylbenzoic acid methyl ester (IX) by means of 3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride (BHMT) and TEA in DMF affords the 1,4-butanedione derivative (X), which is submitted to a pyrrole synthesis by cyclization with AcONH4 in refluxing ethanol to provide the disubstituted pyrrole (XI). Finally, the ester group of (XI) is hydrolyzed with NaOH in ethanol to furnish the target carboxylic acid.