Ethyl Acetate → 3-Methoxy-4-(2-methyl-1,3-oxazol-5-yl)benzoic acid

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, a mixture of zinc cyanide(II) (41.3 g), 5-(4-bromo-2-fluorophenyl)-2-methyl-1,3-oxazole (150 g), tris(dibenzylideneacetone)dipalladium(0) (10.8 g), 1,1′-bis(diphenylphosphino)ferrocene (13.0 g), zinc powder (4.60 g) and N,N-dimethylacetamide (600 mL) was stirred at 120° C. for 1 hr. The reaction mixture was diluted with ethyl acetate (1.4 L), aqueous ammonia (20%, 100 mL) and water (700 mL) were added, and the mixture was filtered through celite. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. To a mixture of the residue in DMF (880 mL) was added dropwise sodium methoxide (28% methanol solution, 170 g) at 0° C., the mixture was stirred at room temperature for 4 hr, and ice water (300 g) was added. The resulting solid was collected by filtration, washed with water, and added to 6N hydrochloric acid (1.3 L). The reaction mixture was heated under reflux for 2 days, and allowed to cool to room temperature. The resulting solid was collected by filtration, washed with water, subjected to azeotropic distillation with toluene and dried under reduced pressure to give the title compound (93.0 g).

Provenance & Evidence