4-Bromobenzoic acid → 1-[2-(4-Bromo-phenyl)-4-isopropyl-oxazol-5-yl]-ethanol

Participants

Reaction Conditions

Reaction Steps

2-(4-Bromo-phenyl)-4-isopropyl-oxazole-5-carboxylic acid ethyl ester A solution of 4-bromo-benzoic acid (34.0 g, 0.169 mol) in DMF (450 mL) is treated at ambient temperature portionwise with NaH (6.4 g, 0.16 mol, 60% oil dispersion). The suspension is heated to 90° C. and 2-chloro-4-methyl-3-oxo-pentanoic acid ethyl ester (27.7 g, 0.144 mol) is added neat. The remaining chloride is washed into the reaction flask using DMF (25 mL). The reaction mixture is stirred for 18 h, cooled, and treated with water (600 mL). The mixture is extracted with EtOAc (750 mL). The organic layer is washed with brine (2×250 mL), dried (Na2SO4), and concentrated to a foam (56 g). This diester is dissolved in acetic acid (500 mL), treated at ambient temperature with ammonium acetate (80 g, 1.0 mol), and heated at 120° C. for 20 h. The reaction mixture is cooled, concentrated, and partitioned between EtOAc (500 mL) and saturated NaHCO3 solution (3×125 mL). The organic layer is dried (Na2SO4), and concentrated. The crude product is purified by silica gel flash chromatography using hexanes:ethyl acetate (6:1) to give the title compound (26.6 g, 55%).

Provenance & Evidence