反应详情

温度

50 °C

To a solution of 6-chloro-2-(4-fluoroindolin-2-yl)pyridin-3-ol (8.53 g, 32.31 mmol) and Glyoxylic acid ethyl ester (6.59 g, 64.59 mmol) in THF (80 mL), MsOH (0.31 g, 3.23 mmol) was added. The mixture was stirred at 50° C. for 2 hours. The mixture was diluted with water and extracted with EtOAc. The organic layer was washed with brine (30 mL), dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using column chromatography (petroleum ether:EtOAc=10:1) to provide ethyl 2-chloro-11-fluoro-12,12a-dihydro-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole-6-carboxylate (10.2 g, yield: 90.3%). 1H-NMR (CDCl3, 400 MHz) δ 7.04˜7.13 (m, 3H), 6.63 (d, J=8.0 Hz, 1H), 6.55 (t, J=8.4 Hz, 1H), 6.03 (s, 1H), 5.09 (d, J=8.8 Hz, 1H), 4.22˜4.34 (m, 2H), 3.73 (d, J=16.4 Hz, 1H), 3.44˜3.51 (m, 1H), 1.29 (d, J=7.2 Hz, 3H). MS (M+H)+: 349.

1. extractionextracted with EtOAc
2. washThe organic layer was washed with brine (30 mL)
3. dry with materialdried over Na2SO4
4. concentrationconcentrated in vacuo
5. customThe resulting residue was purified