Step A: Synthesis of 5-bromo-2-phenoxypyrimidine
5-Bromo-2-iodopyrimidine (Bridge Organics, 1.01 g, 3.57 mmol), phenol (Aldrich, 3.35 g, 35.7 mmol) and potassium carbonate (Aldrich, 4.93 g, 35.7 mmol) were mixed under nitrogen protection and the reaction was stirred for 4 hr at 165°C. Upon completion of the reaction, the mixture was cooled to room temperature, followed by liquid-liquid partition extraction with ethyl acetate (250 mL) and 1N hydrochloric acid (4 × 200 mL). The organic phase was washed with 1N hydrochloric acid until the aqueous phase was colorless. The organic phase was separated and washed sequentially with water (100 mL) and saturated saline (100 mL). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give an orange oily crude product (1.1 g). The crude product was purified by fast silica gel column chromatography using an 80 g Silicycle silica gel column with 10% ethyl acetate in hexane solution as eluent to afford the target compound 5-bromo-2-phenoxypyrimidine as a white solid (0.82 g, 92% yield). Thin layer chromatography (TLC) analysis showed an Rf value of 0.51 (unfolding agent: hexane-ethyl acetate, 8:2 v/v).
Product characterization data:
1H-NMR (400 MHz, CDCl3) δ 8.56 (s, 2H), 7.46-7.41 (m, 2H), 7.30-7.24 (m, 1H), 7.20-7.16 (m, 2H);
Mass spectrum (APCI+) m/z 252.9 (M + 1).
