Ammonia → N-[1-Methyl-1-[6-(trifluoromethyl)-3-pyridinyl]ethyl]acetamide

Participants

Reaction Conditions

Reaction Steps

Add acetonitrile (67.4 L; 53.0 kg) to a reaction vessel containing 2-(6-trifluoromethyl-pyridin-3-yl)-propan-2-ol (52 moles; 12.8 kg) and cool to 0-5° C. Add concentrated sulfuric acid (372 moles; 19.8 L; 36.5 kg) slowly, maintaining the internal reaction temperature between 0-15° C. Heat the solution to 25-30° C. for 24 hours, and observe the completion of the reaction by HPLC. Cool the mixture to 0° C. while stirring and add water (95.0 L; 95.0 kg). Add a solution of aqueous ammonia (57.5 kg) to adjust the solution pH to 8.0-9.0, and then add tert-butyl methyl ether (81.1 L; 60.0 kg). Separate the lower aqueous layer, concentrate the organic layer to approximately 3 volumes, and cool the contents of the reaction to −5-0° C. Filter the resultant solids and dry under vacuum until constant weight and collect (13.4 kg; 87.3%, based on HPLC) of the titled compound as a pale yellow solid in 81.8% purity. 1H NMR (DMSO-d6, 500 MHz): δ 8.68 (d, 1H, J=2 Hz), 8.30 (s, 1H), 7.92 (dd, 1H, J=2.5, 8.5 Hz), 7.79 (d, 1H, J=5.8 Hz), 1.82 (s, 3H), 1.56 (s, 6H).

Provenance & Evidence