Acetic Acid → HCID 86650661, compound

Participants

Reaction Steps

Add HOAc (464 mL, 8.09 mol), 2,5-dimethoxytetrahydrofuran (393 mL, 3.03 mol), water (2.27 L), and trifluoroacetic acid (153 mL, 2.02 mol) sequentially to a solution of (±)-5-phenyl-1-(4-trifluoromethoxy-phenyl)-3-(4-trifluoromethoxy-phenylamino)-1,5-dihydro-pyrrol-2-one (1000 g, 2.02 mol) in THF (8.43 L). Stir the reaction mixture at ambient temperature for 18 hours. Add toluene (4.0 L) and isopropyl acetate (2.0 L). Wash the mixture with water (8.0 L) and saturated sodium hydrogencarbonate solution (6.0 L). Discard the aqueous layer. To the organic layer, add (R)-(+)-α-methyl benzylamine (390 mL, 3.03 mol). Stir the solution at ambient temperature for 3 hours. Concentrate the reaction mixture to obtain a mixture of 1-(4-trifluoromethoxy-phenyl)-3-(R)-1-phenyl-ethylamino)-5(S)-phenyl-1,5-dihydro-pyrrol-2-one and 1-(4-trifluoromethoxy-phenyl)-3-((R)-1-phenyl-ethylamino)-5(R)-phenyl-1,5-dihydro-pyrrol-2-one as a black oil. Dissolve the mixture (888 g, 2.02 mol) in isopropanol (2.0 L) and cool to −7° C. Filter the precipitate and wash with cold isopropanol. Dry under vacuum for 12 hours to give 1-(4-trifluoromethoxy-phenyl)-3-(R)-1-phenyl-ethylamino)-5(R)-phenyl-1,5-dihydro-pyrrol-2-one (130 g, 29%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 7.64 (d, J=8 Hz, 2H), 7.34 (d, J=8 Hz, 2H), 7.24 (m, 4H), 7.11 (m, 4H), 6.98 (d, J=4 Hz, 2H), 5.78 (m, 2H), 5.13 (s, 1H), 4.30 (m, 1H), 1.44 (d, J=4 Hz 3H). LC-MS ESI m/z: 439 (M+H)+, Tr=6.30 min., method 1.

Provenance & Evidence