Acetic Acid → HCID 86650655, compound

Participants

Reaction Conditions

Reaction Steps

Add acetic acid (3.6 mL, 63.2 mmol), 2,5-dimethoxytetrahydrofuran (3.1 mL, 23.7 mmol), and trifluoroacetic acid (2.4 mL, 31.6 mmol) sequentially to a solution of (±) 5-(3-trifluoromethyl-phenyl)-1-(4-trifluoromethoxy-phenyl)-3-(4-trifluoromethoxy-phenylamino)-1,5-dihydro-pyrrol-2-one (8.89 g, 15.8 mmol) in THF (12 mL) and water (3 mL). Heat the reaction mixture to 35° C. for 72 hours. Observe significant formation of (±)-1-(4-trifluoromethoxy-phenyl)-5-(3-trifluoromethyl-phenyl)-pyrrolidine-2,3-dione (LC-MS ESI m/z: 404 (M+H)+, Tr=2.61 min., method 2). Cool the reaction mixture to room temperature and add toluene (20 mL) and isopropyl acetate (10 mL). Wash the mixture with saturated sodium bicarbonate solution and then brine. Filter through sodium sulfate. Add acetic acid (7.6 mL, 126 mmol) and 1-methyl-1-(6-trifluoromethyl-pyridin-2-yl)-ethylamine (4.89 g, 24.0 mmol) to the solution containing (±)-1-(4-trifluoromethoxy-phenyl)-5-(3-trifluoromethyl-phenyl)-pyrrolidine-2,3-dione. Heat to 55° C. for 1.5 hours. Pour reaction mixture into saturated sodium bicarbonate solution and separate phases. Dry over sodium sulfate, filter and concentrated under reduced pressure. Purify by silica gel chromatography (10-50% EtOAc-hexane) to yield the title compound (5.89 g, 63%) as an oil, LC-MS ESI m/z: 588 (M−H)−, Tr=3.55. min., method 2.

Provenance & Evidence