Methyl iodide → N-(6-ethyl-3-methyl-pyridin-2-yl)-2,2-dimethyl-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of N-(6-ethyl-pyridin-2-yl)-2,2-dimethyl-propionamide (24.0 g, 0.116 mol) in diethyl ether (600 mL, 0.2 M) is cooled to −78° C. and treated with tert-butyllithium (144 mL 1.7 M in pentane). After the addition is complete the solution is warmed to −20° C. for 2 h, treated with a solution of methyliodide (23 mL, 0.372 mol) in diethylether (10 mL) and warmed to room temperature. After stirring overnight the reaction is diluted with water, extracted with diethyl ether and dried over MgSO4. The resulting solution is filtered through a short pad of silica gel, concentrated and recrystallized from heptane to give N-(6-ethyl-3-methyl-pyridin-2-yl)-2,2-dimethyl-propionamide (17.6 g, 69%) as an off-white crystalline solid. mp 72-75° C.; Rf 0.43 (50% ethyl acetate in hexanes); 1H NMR (DMSO-d6, 300 MHz) δ 9.48 (s, 1H), 7.53 (d, J=7.8 Hz, 1 H), 7.48 (d, J=7.5 Hz, 1 H), 2.65 (q, J=7.5 Hz, 2 H), 2.02 (s, 3 H), 1.20 (s, 9 H), 1.18 (t, J=7.5 Hz, 3 H); LRMS calcd for C13H20N2O: 220.3; found 220.0 (M)+. Anal. Calcd for C13H20N2O : C, 70.87; H, 9.15; N, 12.72. Found C, 70.70; H, 9.18; N, 12.74.

Provenance & Evidence