Trifluoroacetic acid → HCID 86650870, compound

Participants

Reaction Steps

Add trifluoroacetic acid (7.56 mL, 100 mmol) to a solution of 1-(4-trifluoromethyl-phenyl)-3-[(R)-1-(4-chloro-phenyl)-ethylamino]-5(R)-(3-trifluoromethoxy-phenyl)-1,5-dihydro-pyrrol-2-one (10.8 g, 20.0 mmol) in acetic acid (100 mL) and water (5 mL). Stir at ambient temperature for 60 min. Observe significant formation of (R)-5-(3-trifluoromethoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-pyrrolidine-2,3-dione (LC-MS ESI m/z: 426 (M+Na)+, Tr=2.76 min., method 2). Dilute the reaction with toluene (200 mL) and water (150 mL). Wash the organic layer with water and saturated aqueous sodium bicarbonate solution. Filter the organic layer through sodium sulfate. Add acetic acid (9.17 mL, 160 mmol) and 1-methyl-1-(2-trifluoromethyl-pyrimidin-4-yl)-ethylamine (4.51 g, 22 mmol) to this toluene solution containing (R)-5-(3-trifluoromethoxy-phenyl)-1-(4-trifluoromethyl-phenyl)-pyrrolidine-2,3-dione. Heat to 55° C. for 18 hours. Concentrate reaction mixture under reduced pressure to give a dark purple oil. Purify the residue by silica gel chromatography (25% ethyl acetate-hexane) to obtain (R)-3-[1-methyl-1-(2-trifluoromethyl-pyrimidin-4-yl)-ethylamino]-1-(4-trifluoromethyl-phenyl)-5-(3-trifluoromethoxy-phenyl)-1,5-dihydro-pyrrol-2-one (7.70 g, 65%) as a purple foam. LC-MS ESI m/z: 613 (M+Na)+, Tr=3.35 min., method 2.

Provenance & Evidence