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A round bottom flask, equipped with a magnetic stirrer bar, was charged with 4- methoxycyclohexanone (234.2 mg, 1.8 mmol), ammonium carbonate (140.4 mg, 1.4 mmol) and 2,2,2-trifluoroethanol (4.0 mL). This was stirred at room temperature for 10 mm, thencooled to 0 °C before <strong>[13612-34-5]2-<strong>[13612-34-5](2,5-dimethylphenyl)acetic acid</strong></strong> (200.0 mg, 1.2 mmol) was added. This was stirred an additional 5 mm, and isocyanobenzene (188.4 iL, 1.2 mmol) was added dropwise. The mixture was allowed to warm up to room temperature and stirred for 2 days. A precipitate had formed which was dissolved in dichloromethane. The mixture was evaporated under vacuum and the crude residue was taken up in dichloromethane andpurified by flash column chromatography (DCM/EtOAc) to afford 1-[[2-(2,5- dimethylphenyl)acetyl]amino]-4-methoxy-N-phenyl-cyclohexanecarboxamide (384.2 mg) as a 1.5:1 mixture of diastereoisomers.Major diastereoisomer: 1H NMR (400 MHz, CHLOROFORM-d) oe 9.79 (br. s, 1H), 7.53-7.60 (m, 2H), 7.32 (t, J = 7.5 Hz, 2H), 7.05-7.17 (m, 3H), 7.02 (s, 1H), 5.40 (s, 1H), 3.64 (s, 2H),3.30-3.33 (m, 1H), 3.28 (s, 3H), 2.33 (s, 3H), 2.28 (s, 3H), 2.08-2.15 (m, 2H), 1.89-2.02 (m,2H), 1.73-1.81 (m, 2H), 1.26-1.39 (m, 2H). 13C NMR (CHLOROFORM-d) oe: 13C NMR(CHLOROFORM-d) d: 173.1, 171.3, 138.5, 136.5, 133.7, 132.6, 131.0, 130.9, 129.0, 128.9(2xC), 123.9, 120.0 (2xC), 73.8, 61.1, 55.6, 42.4, 30.1 (2xC), 25.2 (2xC), 20.8, 19.0. LCMS, R0.99 mi (M-H) = 393.Minor diastereoisomer: 1H NMR (400 MHz, CHLOROFORM-d) oe 9.87 (br. s, 1H), 7.54 (dd, J =8.5 Hz, 1.0 Hz, 2H), 7.31-7.36 (m, 2H), 7.06-7.17 (m, 3H), 7.04 (s, 1H), 5.35 (s, 1H), 3.66 (s,2H), 3.35 (s, 3H), 3.13-3.25 (m, 1H), 2.33 (s, 3H), 2.29 (s, 3H), 2.22-2.28 (m, 2H), 1.86-1.98(m, 4H), 1.11-1.26 (m, 2H). 13C NMR (CHLOROFORM-d) oe: 13C NMR (CHLOROFORM-d) d:173.2, 171.4, 138.4, 136.6, 133.7, 132.3, 131.1, 130.9, 129.1, 128.9 (2xC), 124.0, 120.0(2xC), 76.9, 60.9, 55.8, 42.4, 29.8 (2xC), 26.6 (2xC), 20.8, 19.1. LCMS, R 0.97 mi (M-H) =393. |