Ethanol → N-methyl-2-(3-trifluoromethylphenyl)acetamide

Participants

Reaction Conditions

Reaction Steps

At 0° C., 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (21.6 g (0.11 mol) was added to a solution of 3-(trifluoromethyl)phenylacetic acid (Aldrich 19,335-6, 23.0 g, 0.11 mol) and 1-hydroxybenzothiazole (21.6 g, 0.11 mol) in DCM (50 ml) and N,N-dimethylformamide (50 ml). The reaction mixture was stirred for 20 min at 0° C. A 33% solution of methylamine in ethanol (280 ml, 2.25 mol) was added. The reaction mixture was stirred for 56 hours and successively diluted with ethyl acetate (200 ml). It was washed with a 10% aqueous solution of sodium hydrogensulphate (300 ml). The aqueous phase was extracted with ethyl acetate (2×150 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogencarbonate (300 ml) and dried over magnesium sulphate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (300 g), using ethyl acetate/heptane 2:1 as eluent, to give 19.8 g of N-methyl-2-(3-trifluoromethylphenyl)acetamide.

Provenance & Evidence