Cesium carbonate → 2-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-3-fluorophenyl)-N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamide

Participants

Reaction Conditions

Reaction Steps

To a mixture of 2-(benzyloxy)-4-ethoxy-5-iodopyridine (3.2 g, 9.01 mmol) in 1,4-dioxane (60 mL) and water (20 mL) was added N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)-2-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide (6.18 g, 9.91 mmol), Cs2CO3 (5.87 g, 18.02 mmol) and PdCl2(dppf) (0.659 g, 0.901 mmol). The mixture was stirred under nitrogen at 110° C. for 16 h. Then the reaction residue was filtered and the filtrate was concentrated to give the crude product, which was purified by silica column chromatography (PE/EA=5:1). All fractions found to contain product by TLC (PE/EA=5:1, Rf=0.6) were combined and concentrated to yield a light yellow oil of 2-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-3-fluorophenyl)-N-(4-(3-((tert-butyldimethyl silyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamide (4.2 g, 5.21 mmol, 58% yield): 1H NMR (400 MHz, CD3OD) δ 7.96 (d, J=2.0 Hz, 1H), 7.88 (s, 1H), 7.75 (d, J=8.4 Hz, 1H), 7.47 (d, J=6.0 Hz, 3H), 7.42-7.36 (m, 2H), 7.36-7.30 (m, 2H), 7.27-7.17 (m, 2H), 6.50 (s, 1H), 5.38 (s, 2H), 4.16-4.12 (m, 2H), 3.77 (s, 2H), 3.36 (s, 2H), 2.81 (s, 2H), 1.32 (t, J=6.8 Hz, 3H), 0.97 (s, 9H), 0.85 (s, 6H), 0.12 (s, 6H); ES-LCMS m/z 725.2 (M+H).

Provenance & Evidence