反应详情

温度

-78 °C

To a vial charged with 4-(6-fluoro-2H-benzo[b][1,4]oxazin-4(3 H)-yl)-3-methoxybenzonitrile (0.234 g, 0.823 mmol) was added DCM (3.29 ml). The resulting solution was cooled to −78° C. and chlorosulfonic acid (0.137 ml, 2.058 mmol) was added faster than dropwise. After 30 min the mixture was warmed to 0° C. and the mixture was allowed to stir and warm to rt over 3 hr. LC-MS indicated conversion to the desired product mass (M+23). The reaction mixture was added to ice carefully and EtOAc was used to wash reaction vial. The resulting mixture was extracted with EtOAc (2×). The layers were separated and the cloudy aqueous phase was diluted with brine and extracted once more with EtOAc. The combined organics were dried with Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified with a 40 g silicycle HP column ramping EtOAc in heptane (0-50%) providing product 4-(4-cyano-2-methoxyphenyl)-6-fluoro-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride (0.093 g, 0.243 mmol, 29.5% yield) as a light yellow solid. m/z (ESI) 405.2 (M+Na)+.

1. temperatureAfter 30 min the mixture was warmed to 0° C.
2. temperaturewarm to rt over 3 hr