Water → 3-(2-Chlorophenyl)-2-(4-chlorophenyl)-3-oxopropanenitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of (4-chlorophenyl)acetonitrile (15.1 g, 100 mmol) in THF (250 ml) was added NaH (60% dispersion in oil, 8.0 g, 200 mmol) in 3 portions over 5 minutes. To this was added a solution of 2-chlorobenzoic acid ethyl ester (18.3 g, 100 mmol) in THF (50 ml), dropwise over 10 minutes. The mixture was then heated at 60° C. overnight. After cooling to room temperature, water was added (2×10 ml, bubbling observed), and the reaction was concentrated, in vacuo, to ½ volume. The mixture was diluted with water (125 ml) and methylene chloride (125 ml), adjusted to pH=7 with 3 N aqueous HCl, and the aqueous layer separated and extracted with additional methylene chloride. The combined organics were dried (MgSO4) and concentrated, in vacuo, to give a brown oil (33 g) that began to solidify on standing. After stirring the residue overnight in diisopropyl ether (250 ml), the solid product was collected by vacuum filtration to afford, after drying, in vacuo, title product I-3A-1a (15.2 g, 52%) as a tan solid: −ESI MS (M−1) 288.0; 1H NMR (400 MHz, CD2Cl2) δ 7.74 (d, J=8.30 Hz, 1H), 7.60–7.25 (m, 7H), 5.65 (s, 1H).

Provenance & Evidence