4-Piperidinol, 1-methyl- → 6-[(1-Methylpiperidin-4-yl)oxy]pyridine-2-carbonitrile

Participants

Reaction Conditions

Reaction Steps

1-Methylpiperidin-4-ol (1.89 g, 0.0164 mol), 6-bromo-2-pyridinecarbonitrile (3.00 g, 0.0164 mol), Pd(OAc)2 (0.184 g, 0.820 mmol), 2-(di-t-butylphosphino)biphenyl (0.303 g, 1.02 mmol) and Cs(CO3)2 were mixed in 100 mL of toluene. The reaction mixture was stirred under argon and heated to 130° C. in an oil bath for 4 days. The reaction mixture was diluted with EtOAc and washed with water, dried over Na2SO4 and evaporated. The crude product was flash chromatographed on silica gel DCM/MeOH/TEA 95/5/1 to give 1.62 g (45%) of the desired product. 1H NMR (500 MHz, CDCl3) δ 7.67 (m, 1H), 7.29 (d, 1H), 6.95 (d, 1H), 5.12 (m, 1H), 2.74 (m, 2H), 2.40-2.30 (m, 5H, thereof a singlet at 2.35), 2.09 (m, 2H), 1.86 (m, 2H).

Provenance & Evidence