N-Methoxy-N-methylacetamide → 2-(4-Acetyl-2-chlorophenyl)-2-methylpropanenitrile

Participants

Reaction Steps

To a stirred solution of 2-(4-bromo-2-chlorophenyl)-2-methylpropanenitrile (2.85 g, 11.0 mmol) in anhydrous THF (60 mL) at −78° C. is added n-butyllithium (2 M in c-hexane) (60.1 mL, 12.1 mmol). The reaction mixture is stirred at this temperature 10 min., then N-methoxy-N-methyl-acetamide (2.34 mL, 22.0 mmol) is added neat and the solution is stirred 10 min. at −78° C. and then warmed up to room temperature for another hour. Acidic brine (60 mL) is then slowly added and the solution is extracted with EtOAc (3×60 mL). The organic layer is dried over MgSO4, filtered and concentrated under reduced pressure. The crude product is purified by flash chromatography (eluent: Hex/EtOAc 1:0 to 7:3) to provide the expected product 2-(4-acetyl-2-chlorophenyl)-2-methylpropanenitrile (1.57 g, 64%) as a yellow oil. 1H NMR (300 MHz, CHLOROFORM-D): δ 7.96 (1H, d, J=1.9 Hz), 7.81 (1H, dd, J=8.3, 1.9 Hz), 7.55 (1H, d, J=8.3 Hz), 2.56 (3H, s), 1.85 (6H, s).

Provenance & Evidence