4-Bromobenzoic acid → 4-{4-[4-(3-tert-Butyl-phenylcarbamoyl)-2-fluoro-phenyl]-piperazin-1-yl}-benzoic acid

Participants

Reaction Conditions

Reaction Steps

To a N-(3-tert-butyl-phenyl)-3-fluoro-4-piperazin-1-yl-benzamide (0.15 mmol) solution in dioxane was added 4-bromo-benzoic acid (0.195 mmol), NaOtBu (0.45 mmol), Xantphos (0.03 mmol) and Pd2 dba3 (0.009 mmol). The reaction vial was purged with Ar, sealed, and heated at 85° C. overnight. The reaction was worked up by diluting with methanol adding an excess of NH4Cl, and passing through a plug of silica gel (1 g) and eluting with methanol. The methanol fraction was concentrated. The residue suspended in DMSO, filtered, and purified by reverse phase liquid chromatography with increasing concentrations of CH3CN in water yielding the product 4-{4-[4-(3-tert-butyl-phenylcarbamoyl)-2-fluoro-phenyl]-piperazin-1-yl}-benzoic acid. LCMS calcd for C28H30FN3O3 (m/e) 475, obsd 476 (M+H).

Provenance & Evidence