Sulfuric Acid → 1-[4-({3-[2-Benzyl-7-(trifluoromethyl)-2H-indazol-3-YL]phenoxy}methyl)phenyl]cyclopentanecarboxylic 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 (20 mg, 1 eq) with 1-(4-bromomethyl-phenyl)-cyclopentanecarboxylic acid methyl ester (48 mg, 3 eq) and potassium carbonate (37 mg, 5 eq) in acetone (1.5 mL). The latter reagent was obtained by heating 1-p-tolyl-cyclopentanecarboxylic acid in methanol and a catalytic amount of sulphuric acid. Subsequent α-bromination was accomplished by refluxing the ester (100 mg, 1 eq) with NBS (82 mg, 1 eq) and benzoyl peroxide (5 mg, 3%) in carbon tetrachloride (2 mL) for one hour. 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 hydrolyzed with aq LiOH (1M, 40 eq)/THF 1:1 and purified by preparative HPLC, affording the desired product in 48% yleld.

Provenance & Evidence