Methanamine, N-methoxy-, hydrochloride (1:1) → (e)-3-(2-Fluorophenyl)-n-methoxy-n,2-dimethylacrylamide

Participants

Reaction Conditions

Reaction Steps

N,O-dimethylhydroxylamine hydrochloride (7 g, 72 mmol) was slurried in CH2Cl2 (250 mL) and cooled to 0-5° C. A solution of trimethylaluminum (2M in toluene, 36 mL, 72 mmol) was added dropwise. The mixture was warmed to ambient temperature and stirred for 1 hr. A solution of Example 3A (5 g, 24.0 mmol) in CH2Cl2 (100 ml) was added and the solution was heated to reflux overnight. The reaction mixture was cooled in an ice bath and quenched carefully with ice cold 0.5 M HCl. The mixture was filtered through celite filter aid and extracted with CH2Cl2. The organic phase was washed with water and brine, dried over Na2SO4, filtered, and evaporated in vacuo. The crude product was chromatographed (SiO2, 100% hexanes to 20% ethyl acetate/hexanes) to afford the title compound (1.88 g, 35% yield) as a light yellow oil. 1H NMR (300 MHz, CDCl3) δ ppm 7.27-7.38 (m, 2H), 7.04-7.17 (m, 2H), 6.79 (s, 1H), 3.72 (s, 3H), 3.30 (s, 3H), 2.04 (s, 3H). MS (ESI+) 224 (M+H).

Provenance & Evidence