反应详情

温度

8.5 °C

At 50° C., add to a stirring solution of 2-carbomethoxy-3-amino-6-fluoro-benzo[b]thiophene (prepared according to U.S. Pat. No. 5,143,923), (90.1 g, 0.4 mol) in H2O (450 mL), a 50% aqueous solution of NaOH (64 g, 0.8 mol) over 2-3 min. Heat the reaction to 70-73° C. and continue to stir for 3 h. Add 10% aqueous isopropanol (45 mL) and bring to reflux. Remove the isopropanol under N2 and add H2O (300 mL). Cool the reaction mixture to between 7-10° C. and add concentrated HCl (80 mL). Add H2O (650 mL), cool to 5-7° C., filter the resulting solid, and wash the filter cake with H2O (2×150 mL). Dry the solid under vacuum at 35° C. to obtain 80.6 g (94.7%) of solid mp 160-163° C., TLC on silica gel (dichloromethane/methanol, 3:1), Rf=0.69.

1. customprepared
2. temperatureHeat
3. customthe reaction to 70-73° C.
4. temperatureto reflux
5. customRemove the isopropanol under N2
6. additionadd H2O (300 mL)
7. additionadd concentrated HCl (80 mL)
8. temperatureAdd H2O (650 mL), cool to 5-7° C.
9. filtrationfilter the resulting solid
10. washwash the filter cake with H2O (2×150 mL)
11. customDry the solid under vacuum at 35° C.