Acrylonitrile → 1-(4-Methoxy-benzyl)-1H-pyrazol-2-ylamine

Participants

Reaction Conditions

Reaction Steps

Acrylonitrile (7.5 g, 141 mmol) is dissolved in THF (75 mL) and cooled at 0° C. and hydrazine monohydrate (7.41 g, 148 mmol) is added at the same temperature. The reaction mixture is brought to room temperature and stirred for 2 h. p-Anisaldehyde (20.1 g, 148 mmol) is added drop wise and stirred at room temperature for 10 h. The above reaction mixture is then concentrated to result red oil. To the above oil n-BuONa in 80 mL n-BuOH is added drop wise at 0° C. and brought to room temperature. The reaction mixture is heated at 120° C. for 3.5 h. After cooling it is poured onto 300 mL of cold water and extracted with 2×200 mL of Et2O. The ether layer is collected and washed with 3×100 mL of 1N HCl. The combined acidic layer is collected and neutralized with 50% NaOH. The mixture is again extracted with 200 mL of Et2O and washed with water. It is dried (Na2SO4) and concentrated to yield 1-(4-Methoxy-benzyl)-1H-pyrazol-2-ylamine as red oil. MS m/z 204.1 (M+1). Mixture of 1-(4-methoxy-benzyl)-1H-pyrazol-2-ylamine (1 g, 5.0 mmol) and diethyl ethoxymethylenemalonate (1 mL, 5.0 mmol) is heated at 120° C. for 5 h. It is cooled and then the desired compound is isolated by silica gel column chromatography. MS m/z 374.2 (M+1).

Provenance & Evidence