Tetrahydrofuran → 4-(4-(Cyclopropyl(hydroxy)methyl)pyridin-3-yl)-2-methoxybenzonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-(4-formylpyridin-3-yl)-2-methoxybenzonitrile (100 mg, 0.42 mmol) in THF (4 mL) at −36° C. was added 0.5M c-PrMgCl in THF (2.27 mL, 1.13 mmol) dropwise and the mixture was stirred at −36° C. for 1 hr. The mixture was quenched with water at −36° C., silica gel was added, and the mixture was concentrated in vacuo. The residue was purified by silica chromatography eluting with a 40 to 100% EtOAc-heptane gradient. The product obtained was re-purified by Xbridge C18 eluting with a 10 to 100% acetonitrile-water gradient to give 4-(4-(cyclopropyl(hydroxy)methyl)pyridin-3-yl)-2-methoxybenzonitrile. 1H NMR (400 MHz, DMSO-d6) δ ppm −0.13-−0.05 (m, 1H), 0.20-0.29 (m, 1H), 0.29-0.41 (m, 2H), 0.91-1.06 (m, 1H), 3.95 (s, 3H), 4.16 (dd, J=6.6, 4.3 Hz, 1H), 5.39 (d, J=4.5 Hz, 1H), 7.12 (dd, J=7.8, 1.3 Hz, 1H), 7.27 (d, J=1.3 Hz, 1H), 7.66 (d, J=5.3 Hz, 1H), 7.83 (d, J=7.8 Hz, 1H), 8.42 (s, 1H), 8.62 (d, J=5.3 Hz, 1H). HRMS: (ESI) m/z 281.1280 [(M+H)+ Calcd for C17H16N2O2 281.1290].

Provenance & Evidence