Acetic Acid → HCID 86650652, compound

Participants

Reaction Conditions

Reaction Steps

Add HOAc (11.5 mL, 201 mmol), 2,5-dimethoxytetrahydrofuran (9.8 mL, 75.5 mmol), water (56 mL), and trifluoroacetic acid (7.6 mL, 100.6 mmol) sequentially to a solution of (±)-5-(3-trifluoromethoxy-phenyl)-1-(4-trifluoromethoxy-phenyl)-3-(4-trifluoromethoxy-phenylamino)-1,5-dihydro-pyrrol-2-one (29.1 g, 50.3 mmol) in THF (180 mL). Heat the reaction mixture to 35° C. for 22 hours. Observe significant formation of (±)-1-(4-trifluoromethoxy-phenyl)-5-(3-trifluoromethoxy-phenyl)-pyrrolidine-2,3-dione (LC-MS ESI m/z: 420 (M+H)+, Tr=4.23 min., method 1). Cool the reaction mixture to room temperature and add toluene (200 mL) in a single portion. Wash the mixture with water and then pH 9 buffer. Separate layers and observe that the aqueous layer is pH=7. Filter through sodium sulfate and add (R)-(+)-α-methyl benzylamine (12.9 mL, 100.6 mmol). Stir the solution at ambient temperature for 18 hours. Concentrate the reaction mixture and purify by silica gel chromatography (5-15% EtOAc-hexane) to yield 1-(4-trifluoromethoxy-phenyl)-3-(R)-1-phenyl-ethylamino)-5(S)-(3-trifluoromethoxy-phenyl)-1,5-dihydro-pyrrol-2-one (9.01 g, 34%) as a yellow oil, LC-MS ESI m/z: 523 (M+H)+, Tr=5.57 min., method 1 and 1-(4-trifluoromethoxy-phenyl)-3-(R)-1-phenyl-ethylamino)-5(R)-(3-trifluoromethoxy-phenyl)-1,5-dihydro-pyrrol-2-one (11.1 g, 42%) as an orange solid, LC-MS ESI m/z: 523 (M+H)+, Tr=5.49 min., method 1.

Provenance & Evidence