Add acetic acid (6.32 mL, 110 mmol), 2,5-dimethoxytetrahydrofuran (10.7 mL, 82.8 mmol), water (25 mL), and trifluoroacetic acid (4.2 mL, 55.2 mmol) sequentially to a mixture of (±)-4-[5-(3-trifluoromethoxy-phenyl)-2-oxo-3-(4-cyano-phenylamino)-2,5-dihydro-pyrrol-1-yl]-benzonitrile (12.7 g, 27.6 mmol) and THF (83 mL). Heat the reaction mixture to 40° C. for 18 hours. Observe significant formation of (±)-4-[2,3-dioxo-5-(3-trifluoromethoxy-phenyl)-pyrrolidin-1-yl]-benzonitrile (LC-MS ESI m/z: 361 (M+H)+, Tr=2.34 min., method 2). Cool the reaction mixture to room temperature and add toluene (150 mL) in a single portion. Wash the mixture with water and then with brine. Dry over sodium sulfate, filter and add (R)-(+)-α-methyl benzylamine (7.1 mL, 55.2 mmol). Stir the solution at 45° C. for 1.75 hours. Concentrate the reaction mixture and purify by silica gel chromatography (15% EtOAc-hexane) to yield 4-[(S)-2-oxo-3-((R)-1-phenyl-ethylamino)-5-(3-trifluoromethoxy-phenyl)-2,5-dihydro-pyrrol-1-yl]-benzonitrile (3.34 g, 26%) as a red oil, LC-MS ESI m/z: 464 (M+H)+, Tr=3.09 min., method 2 and 4-[(R)-2-oxo-3-((R)-1-phenyl-ethylamino)-5-(3-trifluoromethoxy-phenyl)-2,5-dihydro-pyrrol-1-yl]-benzonitrile (4.05 g, 32%) as a foam, LC-MS ESI m/z: 464 (M+H)+, Tr=3.04 min., method 2.
