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

Participants

Reaction Steps

To a stirred solution of 2-(4-bromo-3-methylphenyl)-2-methylpropanenitrile (5.0 g, 21.0 mmol) in anhydrous THF (75 mL) at −100° C. is added n-butyllithium (2 M in c-hexane) (21 mL, 42 mmol). This reaction mixture is stirred at that temperature 5 min., then N-methoxy-N-methyl-acetamide (4.33 g, 42 mmol) is added. The solution is then warmed up to room temperature over 1 h. Acidic brine (30 mL of brine, 15 mL of 3% HCl aq) is then slowly added and the solution is extracted with EtOAc (3×100 mL). The organic layer is dried over MgSO4, filtered and concentrated under reduced pressure. The crude product is purified on silica gel using a 0 to 30% gradient of EtOAc in heptane to provide the expected product 2-(4-acetyl-2-methylphenyl)-2-methylpropanenitrile (1.0 g, 24%). 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.71 (s, 6 H) 2.53 (s, 3H) 2.56 (s, 3H) 7.30-7.38 (m, 2H) 7.70 (d, J=8.01 Hz, 1H)

Provenance & Evidence