To a solution of 4-[(4-acetylpiperazin-1-yl)methyl]-2-chloro-3-fluoropyridine (14-3, 85 mg, 0.31 mmole) in dry toluene (2 mL) was added NaOtBu (42 mg, 0.44 mmole), racemic BINAP (29 mg, 0.05 mmole), Pd2(dba)3 (14 mg, 0.02 mmole), and benzophenone imine (0.06 mL, 0.38 mmole) then the mixture was heated to 80° C. After 18 hr the mixture was cooled to RT. A solution of 1N HCl:THF (1:1, 10 mL) was added and the mixture stirred for 1 hr. The mixture was washed with EtOAc (2×). The aqueous layer was made basic with saturated NaHCO3 then extracted with EtOAc (3×). The combined organic layers were dried (Na2SO4), filtered, and concentrated. Flash column chromatography (gradient, 0-5% MeOH/CH2Cl2) gave the titled compound as a light yellow solid: 1H-NMR (500 MHz, CDCl3) δ 7.81 (d, 1 H, J=5.12 Hz), 6.71 (t, 1 H, J=4.88 Hz), 4.56 (bs, 2 H), 3.63 (t, 2 H, J=5.13 Hz), 3.56 (s, 2 H), 3.10 (t, 2 H, J=5.13 Hz), 2.46 (m, 2 H), 2.08 (s, 3 H); MS (ES) (M+H)+ 253.
