反应详情

To a solution of the methyl [(4-amino-5′-isopropyl-2′-methoxybiphenyl-2-yl)methyl][3,5-bis(trifluoromethyl)benzyl]carbamate from Example 9 (0.31 g, 0.56 mmol) in chloroform (10 ml), n-amyl nitrite (0.11 ml, 0.84 mmol) and iodine (0.28 g, 1.1 mmol) were added. The mixture was heated to and maintained at reflux for 2 h. TLC analysis (5:95 EtOAc/hexane) showed completion of the reaction. The mixture was diluted with methylene chloride (20 ml) and washed with saturated sodium thiosulfate solution, brine. The light yellow solution was dried over sodium sulfate. The title compound was obtained by flash column chromatography using 5:95 EtOAc/hexane as the eluant. 1H NMR (CDCl3, 500 MHz) δ 7.74 (s, 1H), 7.67 (dd, J=8.0, 2.0 Hz, 1H), 7.47 (m, 1H), 7.31 (dd, J=8.0, 2.0 Hz, 1H), 7.21 (d, J=8.0 Hz, 1H), 7.16 (d, J=8.5 Hz, 1H), 6.95 (d, J=8.0 Hz, 1H), 6.91 (dd, J=4.0, 2.5 Hz, 1H), 6.87 (d, J=8.5 Hz, 1), 4.20-4.48 (m, 4H), 3.78 (s, 3H), 3.70 (s, 3H), 2.92 (m, 1H), 1.23 (s, 3H), 1.21 (s, 3H), LC-MS (M+1) 666.0 (4.74 min).

1. temperatureThe mixture was heated to and
2. temperaturemaintained
3. temperatureat reflux for 2 h
4. customcompletion of the reaction
5. washwashed with saturated sodium thiosulfate solution, brine
6. dry with materialThe light yellow solution was dried over sodium sulfate