Reaction Steps
The diacetoxypalladium (11.3 mg, 0.05 mmol) was added to a argon purged and degassed solution of (S)-isopropyl 2-(4-(4-benzylpiperidin-1-yl)-5-bromo-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (267 mg, 0.502 mmol), 2-(4-(4-fluorophenethoxy)phenyl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione (205 mg, 0.553 mmol), and 2-dicyclohexylphosphino-2′,6′-dimethoxy-biphenyl (41 mg, 0.10 mmol), and potassium phosphate tribasic (800 mg, 3.77 mmol) in dioxane (4 mL) and water (0.8 mL) and stirred in a screw-capped pressure vessel for 16 h at 90° C. The reaction was allowed to cool, diluted with EtOAc, and the organic layer was washed with brine and dried (MgSO4). The crude product was charged (DCM) to a 40 g ISCO silica gel cartridge and gradient elution (0-35% EtOAc/hexanes) using an Isolera chromatography station gave (S)-isopropyl 2-(4-(4-benzylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate 131 mg (39%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.43-7.37 (m, 2H), 7.24-7.22 (m, 2H), 7.18-7.12 (m, 4H), 7.10 (t, J=7.3 Hz, 2H), 6.99-6.92 (m, 3H), 5.92 (s, 1H), 4.97-4.92 (m, 1H), 4.21 (t, J=6.2 Hz, 2H), 3.37-3.37 (m, 4H), 3.06 (t, J=6.2 Hz, 2H), 2.46 (br. s, 2H), 2.42 (s, 3H), 2.02 (s, 3H), 1.70 (t, J=8.8 Hz, 1H), 1.45-1.43 (m, 1H), 1.37-1.34 (m, 1H), 1.29-1.22 (m, 2H), 1.18 (d, J=6.2 Hz, 3H), 1.14 (d, J=3.2 Hz, 3H), 1.09 (m, 9H). UPLC (M+H)=667.5.
