反应详情

温度

25 °C

A solution of (4S,5R)-3-{[3-(5-amino-2-methoxyphenyl)-6-azetidin-1-ylpyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (460 mg, 0.792 mmol) in toluene (7 mL) and diiodomethane (2 mL, 24.79 mmol) was added isoamyl nitrite (0.213 mL, 1.585 mmol) dropwise at room temperature. The mixture was stirred at 25° C. for 15 min. Then the mixture was heated at 80° C. for 45 min. The reaction mixture was loaded on a silica column directly and was purified by flash chromatography (Biotage Horizon, 25M, Si, ˜20 mL/min, 100% hexanes for 270 mL, gradient to 35% EtOAc in hexanes over 972 mL) to afford (4S,5R)-3-{[6-azetidin-1-yl-3-(5-iodo-2-methoxyphenyl)pyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one. LCMS calc.=691.1. found=692.0 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 7.87 (s, 1H); 7.75 (s, 2H); 7.62 (dd, J=8.7, 2.2 Hz, 1H); 7.54-7.38 (m, 1H); 7.29 (d, J=8.3 Hz, 1H); 6.74 (d, J=8.7 Hz, 1H); 6.28 (d, J=8.3 Hz, 1H); 5.75-5.30 (m, 1H); 4.81 (d, J=16.3 Hz, 1H); 4.21-4.00 (m, 6H); 3.79 (s, 3H); 2.48-2.38 (m, 2H); 0.67 (s, br, 3H).

1. temperatureThen the mixture was heated at 80° C. for 45 min
2. customwas purified by flash chromatography (Biotage Horizon, 25M, Si, ˜20 mL/min, 100% hexanes for 270 mL, gradient to 35% EtOAc in hexanes over 972 mL)