Trifluoroacetic acid → HCID 86650670, compound

Participants

Reaction Steps

Add trifluoroacetic acid (2.00 mL, 26.43 mmol) to a biphasic mixture of 4-[(R)-2-oxo-3-((R)-1-phenyl-ethylamino)-5-(3-trifluoromethoxy-phenyl)-2,5-dihydro-pyrrol-1-yl]-benzonitrile) in dichloromethane (12 mL) and water (4.9 mL). Stir at ambient temperature for 2 hours. Observe significant formation of 4-[(R)-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. Wash the reaction mixture with water. Filter the organic phase through sodium sulfate and add 1-methyl-1-(6-trifluoromethyl-pyridin-2-yl)-ethylamine (1.30 g, 6.35 mmol). Heat to reflux temperature for 18 hours. Partially concentrate reaction mixture and place on a silica gel chromatography column. Purify by silica gel chromatography (25% ethyl acetate-hexane) to obtain 4-[(R)-3-[1-methyl-1-(6-trifluoromethyl-pyridin-2-yl)-ethylamino]-2-oxo-5-(3-trifluoromethoxy-phenyl)-2,5-dihydro-pyrrol-1-yl]-benzonitrile (1.06 g, 37%). 1H NMR (400 MHz, CDCl3) δ 7.71 (t, J=7.9 Hz, 1H), 7.64-7.61 (m, 2H), 7.59 (d, J=7.9 Hz, 1H), 7.53-7.44 (m, 4H), 7.26-7.24 (m, 1H), 7.04-6.96 (m, 2H), 6.80 (s, 1H), 5.38 (d, J=2.6 Hz, 1H), 4.99-4.97 (m, 1H), 4.69 (d, J=2.6 Hz, 1H), 1.65 (d, J=7.5 Hz, 6H).

Provenance & Evidence