Sodium Carbonate → 1,1-Dimethylethyl 4-[({6-[4-(methylsulfonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

The title compound was prepared as a white solid from [4-(methylsulfonyl)phenyl]boronic acid (0.44 g, 2.15 mmol), 1,1-dimethylethyl 4-{[(6-chloro-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate (0.54 g, 1.65 mmol), 2M Na2CO3 (5 mL) and PdCl2(PPh3)2 (0.12 g) in DMF (20 mL). The reaction mixture was heated at 85° C. under N2 for 5 h, then cooled to ambient temperature, and extracted with EtOAc (70 mL×2). The combined organic extracts were washed with water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a gray solid. The crude product was purified by chromatography on a silica gel column eluted with 25% EtOAc/CH2Cl2 to give the title compound (0.44 g, 60%) as a white solid. 1H NMR (400 MHz, CD3OD): δ 8.36 (d, 1H, J=2.9 Hz), 8.18 (d, 2H, J=8.6 Hz), 8.02 (d, 2H, J=8.3 Hz), 7.92 (d, 1H, J=8.8 Hz), 7.49 (dd, 1H, Ja=8.8 Hz, Jb=2.9 Hz), 4.20-4.10 (m, 2H), 3.99 (d, 2H, J=6.3 Hz), 3.15 (s, 3H), 2.90-2.75 (m, 2H), 2.10-2.00 (m, 1H), 1.90-1.80 (m, 2H), 1.46 (s, 9H), 1.35-1.25 (m, 2H); LRMS (ESI), m/z 447 (M+H).

Provenance & Evidence