Sodium hydride → 3-[(1-Methylpiperidin-3-yl)oxy]benzonitrile

Participants

Reaction Conditions

Reaction Steps

1-Methylpiperidin-3-ol (500 mg, 4.341 mmol) was dissolved in DMF (10 ml) and cooled to 0° C. NaH (312 mg, 6.52 mmol) was added in small portions, stirred for 30 minutes and 3-fluorobenzonitrile (557 μl, 5.21 mmol) was subsequently added. The mixture was allowed to reach r.t. over 1 h and stirred for a further 16 h. Cooled to 0° C. and quenched with water. The reaction mixture was separated between water (150 ml) and DCM (2×150 ml). The combined organics were washed with water (150 ml), dried through a phase separator and evaporated in vacuo. Purification by flash silica gel chromatography using a 40 g Biotage column with a gradient of 10-100% EtOAc/MeOH/TEA 100:10:1 in heptane yielded the title compound as a colorless oil. Yield: 0.628 g (56%). 1H NMR (400 MHz, CDCl3) δ 7.32 (dt, 1H, J=7.6 Hz, J=0.9 Hz), 7.19 (m, 1H), 7.16-7.11 (m, 2H), 4.36 (m, 1H, J=4.0 Hz), 2.84 (m, 1H), 2.55 (m, 1H), 2.30-2.11 (m, 5H), 1.94 (m, 1H), 1.82 (m, 1H), 1.67-1.43 (m, 2H).

Provenance & Evidence