The title compound was prepared by solid-phase synthesis on a Sasrin resin. The silylated m-hydroxyphenylacetic acid (I) was attached to the resin using DCC and DMAP to yield the acid-bound resin (II). The silyl group of (II) was then removed by treatment of resin (II) with tetrabutylammonium fluoride in THF. The resultant phenol (III) was coupled to 3-bromo-1-propanol (IV) under Mitsunobu conditions to afford the bromide functionalized resin (V). Displacement of the bromide ion of (V) with 2,2-diphenylethylamine (VI) furnished the secondary amine (VII), which was subjected to reductive alkylation with aldehyde (VIII) in the presence of NaBH(OAc)3 to produce the resin-bound product (IX). Cleavage from the solid support employing trifluoroacetic acid in CH2Cl2 provided the target carboxylic acid.
In a solution-phase synthesis, 2,2-diphenylethylamine (VI) was reductively condensed with 2-chloro-3-(trifluoromethyl)benzaldehyde (VIII) using a polymer-supported borohydride resin to give the secondary amine (X). Mitsunobu coupling of methyl 3-hydroxyphenylacetate (XI) with 3-bromo-1-propanol (IV) afforded the bromopropyl ether (XII). Condensation of bromide (XII) with amine (X) in refluxing acetonitrile furnished amino ester (XIII). This was finally hydrolyzed with LiOH to the title carboxylic acid.