Methyl iodide → 2-Methyl-4-(trifluoromethoxy)benzamide

Participants

Reaction Conditions

Reaction Steps

To a solution of N-Propenyl-4-trifluoromethoxy-benzamide 12 (8.0 g, 33 mmol) in THF (100 mL) at −78° C. was added n-butyllithium (29 mL, 72 mmol of a 2.5 M solution in hexanes). The reaction mixture was warmed to −30° C. for 10 min and cooled back to −78° C. A solution of MeI (2.24 mL, 33 mmol) in THF (5 mL) was slowly added to the reaction mixture. The cooling bath was removed and once the reaction temperature warmed to 0° C., 3 N HCl (10 mL) was added and the resulting two phase mixture heated to 60° C. for 1 h. Upon completion of reaction, the solution was neutralized with aqueous sodium bicarbonate and extracted with ether. The combined organic layers were dried (sodium sulfate) and concentrated. The residue was purified by ether/hexane triturated to provide the title compound (colorless solid 75%). 1H NMR (400 MHz,CDCl3) δ7.50 (d, J=8.4 Hz, 1 H, Ar), 7.09 (m, 2 H, Ar), 5.74 (broad s, 2 H, NH2), 2.52 (s, 3 H, CH3)

Provenance & Evidence