Cesium carbonate → N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoro methyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-3-fluorophenyl) acetamide

Participants

Reaction Steps

A solution of 2-(4-bromo-3-fluorophenyl)-N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)acetamide (80 mg, 0.139 mmol), 3-ethoxy-2-((4-methoxybenzyl)oxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (53.5 mg, 0.139 mmol), Cs2CO3 (90 mg, 0.278 mmol), PdCl2(dppf) (10.15 mg, 0.014 mmol) in 1,4-dioxane (9 mL) and H2O (3 mL) was stirred at 110° C. for 15 min. After LCMS analysis showed the starting material had disappeared, the solvent was removed in vacuo. The residue was dissolved in EA (60 mL) and washed with H2O (20 mL) and brine (20 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by preparative TLC (PE/EA=2/1) to yield N-(4-(3-((tert-butyldimethylsilyl)oxy)-2,2-dimethylpropyl)-3-(trifluoromethyl)phenyl)-2-(4-(5-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-3-fluorophenyl)acetamide (100 mg, 0.111 mmol, 80.0% yield): 1H NMR (400 MHz, CD3OD) δ 7.84 (d, J=2.0 Hz, 1H), 7.77 (s, 1H), 7.37 (d, J=7.6 Hz, 1H), 7.34-7.30 (m, 5H), 7.17-7.15 (m, 2H), 6.83 (d, J=8.8 Hz, 2H), 5.27 (s, 2H), 4.04-3.99 (m, 4H), 3.70 (s, 3H), 3.66 (s, 2H), 3.24 (s, 2H), 2.69 (s, 2H), 1.31 (t, J=7.0 Hz, 3H), 0.86 (s, 9H), 0.73 (s, 6H), 0.00 (s, 6H); ES-LCMS m/z 755.2 (M+H).

Provenance & Evidence