Dichloromethane → HCID 86674840, compound

Participants

Reaction Conditions

Reaction Steps

To the solution of 2-difluoromethoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (927 mg, 3.14 mmol), 1-(3-Bromo-pyridin-4-yl)-ethanol (634 mg, 3.14 mmol) and PdCl2(dppf). CH2Cl2 adduct (256 mg, 0.31 mmol) in DMF (12 mL) was added a solution of Na2CO3 (2M, 3.14 ml, 6.28 mmol) under Nitrogen atmosphere. The mixture was stirred and heated at 100° C. for 6 hrs. After letting cool to room temperature, solvent was removed in vacuo. The resulting residue was dissolved in DCM and saturated NH4Cl solution. After extraction with DCM and separation, the combined extracts were concentrated and the residue was purified by ISCO 40 g (EtOAc/Heptane, v/v, 0-90%) to give 4-[5-Chloro-4-(1-hydroxy-ethyl)-pyridin-3-yl]-2-difluoromethoxy-benzonitrile (290 mg, 32%) as a white solid; ESI-MS m/z: 291 [M+1]+, Retention time 1.28 min; 1H-NMR (CDCl3, 400 MHz) δ 1.41 (d, J=6.8 Hz, 3H), 4.92 (q, J=6.8 Hz, 1H), 6.72 (t, J=71.2 Hz, 1H), 7.31 (dd, J=8.0, 1.2 Hz, 1H), 7.36 (d, J=1.2 Hz, 1H), 7.70 (d, J=5.2 Hz, 1H), 7.79 (d, J=8.0 Hz, 1H), 8.44 (s, 1H), 8.71 (d, J=5.2 Hz, 1H).

Provenance & Evidence