Reaction Steps
A mixture of (S)-isopropyl 2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (1.0 g, 2.13 mmol), 2-(4-(4-fluorophenethoxy)phenyl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione (0.87 g, 2.434 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.175 g, 0.426 mmol) and 2M K3PO4 (7.99 mL, 15.98 mmol) in 1,4-Dioxane (200 mL) and Water (40.0 mL) was degassed for 10 min. Then, PdOAc2 (0.048 g, 0.213 mmol) was added, degassed for 5 min and mixture was heated at 80° C. for 3 h. After cooling to room temp, water was added and the mixture was extracted with ethyl acetate, washed with brine, dried (Na2SO4), filtered and concentrated the residue was then purified by Biotage (5-40% EtOAc/hexane) to afford (S)-isopropyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (1.056 g, 82% yield) as white foam. 1H NMR (500 MHz, CDCl3) δ 7.32-7.26 (m, 2H), 7.18-7.14 (m, 1H), 7.09-7.01 (m, 3H), 6.99-6.93 (m, 2H), 6.07 (br. s., 1H), 5.10 (spt, J=6.2 Hz, 1H), 4.28-4.19 (m, 2H), 3.21 (d, J=12.0 Hz, 1H), 3.13 (t, J=6.9 Hz, 2H), 2.87 (t, J=12.1 Hz, 1H), 2.60 (s, 3H), 2.28 (d, J=12.8 Hz, 1H), 2.20 (s, 3H), 2.10-2.01 (m, 1H), 1.60-1.52 (m, 1H), 1.42-1.34 (m, 1H), 1.25 (d, J=6.3 Hz, 3H), 1.23 (d, J=6.3 Hz, 3H), 1.20 (s, 9H), 1.08 (d, J=12.3 Hz, 1H), 0.91 (s, 3H), 0.66 (s, 3H). 1H of piperidine was not resolved. LCMS (M+H)=606.5.
