Sodium Carbonate → 3-{4-[1-(2-Biphenyl-4-yl-4-isopropyl-oxazol-5-yl)-ethoxy]-2-methyl-phenyl}-propionic Acid

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

A solution of 3-(4-{1-[2-(4-bromo-phenyl)-4-isopropyl-oxazol-5-yl]-ethoxy}-2-methyl-phenyl)-propionic acid methyl ester (150 mg, 0.308 mmol) in toluene (4 ml) and THF (0.5 ml) is bubbled with nitrogen for 10 minutes. To this solution is added phenyl boronic acid (56 mg, 0.46 mmol), Pd(OAc)2 (10 mg), and sodium carbonate (1.0 ml, 2.0 N). The suspension is heated to 85° C. for 8 hours and the mixture is then extracted with EtOAc (3×10 mL). The combined organics are dried over Na2SO4 and concentrated, purified by silica gel chromatography (Hexanes/EtOAc, 7.5/2.5) to afford the biphenyl intermediate as a colorless oil. The ester is then dissolved in MeOH (1.0 ml) and THF (0.5 ml) and treated with NaOH (2.0 N, 1.5 ml). The mixture is stirred at room temperature for 2 hours and concentrated to an aqueous residue. It is then neutralized with 5 N HCl to pH˜4 and extracted with EtOAc (3×5 ml). The combined organics are dried over Na2SO4 and concentrated, purified by silica gel chromatography (Hexanes/EtOAc, 5/5, then Hexanes/EtOAc/HOAc 5/5/0.02) to afford the acid as a colorless oil (35 mg, 24%). MS (ES): 470.1 (M++1).

Herkunft & Nachweise