Methanamine, N-methoxy-, hydrochloride (1:1) → (e)-3-(4-Fluorophenyl)-n-methoxy-n,2-dimethylacrylamide

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Reaction Steps

A mixture of Example 1B (16.1 g, 89.4 mmol), N,O-dimethylhydroxylamine hydrochloride (9.15 g, 93.9 mmol), 1-hydroxybenzotriazole hydrate (12.7 g, 93.9 mmol), 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (17.9 g, 93.9 mmol), and diisopropylethyl amine (47.4 g, 370 mmol) was stirred in DMF (400 mL) at ambient temperature overnight. The solution was diluted with water and extracted with ethyl acetate. The organic phase was washed with saturated sodium bicarbonate solution, 1N HCl, water, brine, dried over Na2SO4, and evaporated in vacuo. The resulting material was chromatographed (SiO2, 20% ethyl acetate/hexanes to 50% ethyl acetate/hexanes) to yield the title compound (16.89 g, 58% yield) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ ppm 7.33 (dd, J=8.82, 5.43 Hz, 2H), 7.00-7.14 (m, 2H), 6.79 (s, 1H), 3.70 (s, 3H), 3.29 (s, 3H), 2.11 (s, 3H). MS (DCI+) 224 (M+H).

Provenance & Evidence