Reaction Steps
A 100-mL three-neck round-bottomed flask equipped with a magnetic stirrer, nitrogen inlet and reflux condenser was charged with 122d (550 mg, 1.19 mmol), 122e (255 mg, 1.19 mmol), cesium carbonate (860 mg, 2.64 mmol) and 1,4-dioxane (20 mL). After bubbling nitrogen through the resulting mixture for 20 minutes, Xantphos (59.0 mg, 0.102 mmol) and tris(dibenzylideneacetone)dipalladium(0) (55.0 mg, 0.06 mmol) were added, and the reaction mixture was heated at reflux for 5 h. After this time, the reaction was cooled to room temperature, filtered and concentrated under reduced pressure to afford a brown residue. Another 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with residue obtained above, THF (10 mL), ethanol (10 mL), water (10 mL) and lithium hydroxide (115 mg, 4.80 mmol). The mixture was stirred at 50° C. for 2 h. After this time, the reaction mixture was concentrated under reduced pressure. The resulting residue was purified by flash chromatography to afford a 23% (165 mg) yield of 122 as a white solid: mp 171-172° C.; 1H NMR (500 MHz, DMSO-d6) δ 8.66 (d, 1H, J=2.0 Hz), 8.57 (s, 1H), 7.72 (d, 1H, J=8.5 Hz), 7.71 (s, 1H), 7.61 (d, 1H, J=8.0, 1.5 Hz), 7.54 (d, 1H, J=9.5 Hz), 7.50 (t, 1H, J=8.0 Hz), 7.45 (dd, 1H, J=8.0, 1.5 Hz), 7.38-7.36 (m, 2H), 7.30 (d, 1H, J=9.5 Hz), 4.94 (s, 2H), 4.84 (t, 1H, J=5.0 Hz), 4.34 (d, 2H, J=5.0 Hz), 3.60 (s, 3H), 3.41 (t, 4H, J=5.0 Hz), 2.39 (t, 4H, J=5.0 Hz), 2.20 (s, 3H), 1.36 (s, 9H); MS (ESI+) m/z 594.3 (M+H).
