Dichloromethane → 4-[5-Chloro-4-(1-hydroxy-ethyl)-pyridin-3-yl]-2-methoxy-benzonitrile

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Reaction Conditions

Reaction Steps

To the solution of 2-Methoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (570 mg, 2.20 mmol), 1-(3-Bromo-5-chloro-pyridin-4-yl)-ethanol (520 mg, 2.20 mmol) and PdCl2(dppf). CH2Cl2 adduct (65 mg, 0.08 mmol) in DMF (10 mL) was added Na2CO3 solution (2M in eater, 2.75 ml, 5.50 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 residue was dissolved in DCM and saturated NH4Cl solution. After extraction with DCM and separation, the combined extracts were concentrated and purified by ISCO 40 g (10% MeOH/DCM, v/v, 0-25%) to give 4-[5-Chloro-4-(1-hydroxy-ethyl)-pyridin-3-yl]-2-methoxy-benzonitrile (320 mg, 50%) as colorless solid; ESI-MS m/z: 289 [M+1]+, Retention time: 1.30 min; 1H-NMR (MeOD, 400 MHz) δ 1.55 (d, J=6.8 Hz, 3H), 4.01 (s, 3H), 5.13 (q, J=6.8 Hz, 1H), 7.07 (dd, J=8.0, 2.0 Hz, 1H), 7.19 (d, J=2.0 Hz, 1H), 7.73 (d, J=8.0 Hz, 1H), 8.31 (s, 1H), 8.61 (s, 1H).

Provenance & Evidence