Sodium Carbonate → 1,1-Dimethylethyl 4-({[6-(4-bromo-2-fluorophenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

4-Bromo-2-fluorobenzeneboronic acid (0.69 g, 3.10 mmol) was added to a solution of 1,1-dimethylethyl 4-{[(6-bromo-3-pyridinyl)oxy]methyl}-1-piperidinecarboxylate (1.0 g, 2.70 mmol) in DME (30 mL), followed by addition of 2M Na2CO3 (8 mL) and Pd(PPh3)4 (0.16 g, 0.13 mmol). The reaction mixture was degassed with N2 and heated at 80° C. for 4 h, then cooled to ambient temperature. Water was added and the mixture was extracted with EtOAc (70 mL×2). The combined organic extract was washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product. The crude product was purified by chromatography on a silica gel column eluted with 1:5 EtOAc/hexanes to give 0.785 g (63%) of 1,1-dimethylethyl 4-({[6-(4-bromo-2-fluorophenyl)-3-pyridinyl]oxy}methyl)-1-piperidinecarboxylate as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 8.38 (d, 1H, J=2.6 Hz), 7.90-7.85 (m, 1H), 7.75-7.65 (m, 1H), 7.40-7.30 (m, 2H), 7.30-7.20 (m, 1H), 4.18 (bs, 2H), 3.89 (d, 2H, J=6.3 Hz), 2.85-2.70 (m, 2H), 2.05-1.95 (m, 1H), 1.90-1.80 (m, 2H), 1.46 (s, 9H), 1.35-1.25 (m, 2H); LRMS m/z 465/467 (M+H).

Provenance & Evidence