To the solution of 2-Chloro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (263 mg, 1.00 mmol), 1-(3-Bromo-5-Fluoro-pyridin-4-yl)-ethanol (220 mg, 1.00 mmol) and PdCl2(dppf). CH2Cl2 adduct (65 mg, 0.08 mmol) in DMF (4 mL) was added 2M Na2CO3 solution (1.50 ml, 3.00 mmol) under nitrogen atmosphere. The mixture was stirred and heated at 100° C. for 4 hrs. After letting cool to room temperature, solvent was removed in vacuo. The resulting residue was dissolved in DCM and sat. NH4Cl solution. After extraction with DCM, the combined extracts were concentrated and purified by ISCO 12 g (0-30% EtOAc/Hep) to give 2-Chloro-4-[5-fluoro-4-(1-hydroxy-ethyl)-pyridin-3-yl]-benzonitrile (138 mg, 49%) as a white solid; ESI-MS m/z: 276 [M+1]+, Retention time 1.15 min. 1H-NMR (CDCl3, 400 MHz) δ 1.53 (d, J=6.8 Hz, 3H), 4.76 (q, J=6.8 Hz, 1H), 7.28 (dd, J=8.0, 2.0 Hz, 1H), 7.45 (d, J=2.0 Hz, 1H), 7.71 (d, J=8.0 Hz, 1H), 8.20 (s, 1H), 8.46 (d, J=2.0 Hz, 1H). The racemate was separated by chiral HPLC (ChiralPak IA-H, 40% EtOH/Heptane, v/v) and yielded 2-Chloro-4-[5-fluoro-4-((R)-1-hydroxy-ethyl)-pyridin-3-yl]-benzonitrile 16-(enantiomer-1) (retention time: 5.24 min) and 2-Chloro-4-[5-fluoro-4-((S)-1-hydroxy-ethyl)-pyridin-3-yl]-benzonitrile 16-(enantiomer-2) (retention time: 13.69 min).
