Sulfuric Acid → 2-[4-({3-[2-Benzyl-7-(trifluoromethyl)-2H-indazol-3-YL]phenoxy}methyl)phenyl]-2-methylpropanoic acid

Participants

Reaction Steps

This compound was prepared similarly to that of Example 525 by treating 3-(2-benzyl-7-trifluoromethyl-2H-indazole-3-yl)-phenol (23 mg, 1 eq) with 2-(4-bromomethyl-phenyl)-2-methyl-propionic acid methyl ester (17 mg, 1 eq) and potassium carbonate (26 mg, 3 eq) in acetone (2 mL). The latter reagent was obtained by heating p-tolyl-acetic acid in methanol and a catalytic amount of sulphuric acid. Subsequent methylation was accomplished by treating the obtained ester (50 mg, 1 eq) with sodium hydride (26 mg, 2.2 eq) and methyl iodide (41 μL, 2.2 eq) in THF (1 mL). Then α-bromination was accomplished by refluxing the ester (16 mg, 1 eq) with NBS (15 mg, 1 eq) and benzoyl peroxide (1 mg, 3%) in carbon tetrachloride (1.5 mL) overnight. The reaction mixture was cooled, water was added and product extracted with dichloromethane. The residue was purified by flash chromatography (ethyl acetate/n-heptane, 1:9, as an eluent). Then the resulting compound was then hydrolyzed with aq LiOH (1M, 40 eq)/THF, 1:1, and purified by preparative HPLC, affording the desired product in 26% yleld.

Provenance & Evidence