反应详情

温度

110 °C

The crude product from step (ii) above was dissolved in warm toluene (150 mL) and treated with anhydrous methanesulfonic acid (50 mL). Toluene (105 mL) was removed from the mixture by distillation at reduced pressure (28 mbar). The remaining mixture was then heated to 110° C. for 6.5 h. The mixture was allowed to cool to 30° C. and the remaining toluene removed by distillation under reduced pressure (25 mbar). The mixture was cooled in an ice/water bath to 40° C. and then treated with water (100 mL), which caused the internal temperature to rise to 70° C. After cooling to 20° C. dichloromethane (80 mL) was added. The mixture was basified by the portionwise addition of aqueous sodium hydroxide solution (10 M, 80 mL), such that the internal temperature remained below 300° C. This took 20 minutes. The dicholoromethane layer was separated and evaporated nearly to dryness in vacuo. Methanol (50 mL) was added and the solvent was again removed in vacuo. The resulting solid was suspended in MeOH (50 mL) and filtered. The filter cake was washed with methanol (20 mL) and the resulting solid dried by air suction to give the title compound as a white crystalline solid (3.46 g, 15% over 3 steps).

1. customToluene (105 mL) was removed from the mixture by distillation at reduced pressure (28 mbar)
2. temperatureto cool to 30° C.
3. customthe remaining toluene removed by distillation under reduced pressure (25 mbar)
4. temperatureThe mixture was cooled in an ice/water bath to 40° C.
5. additiontreated with water (100 mL), which
6. customto rise to 70° C
7. temperatureAfter cooling to 20° C. dichloromethane (80 mL)
8. additionwas added
9. additionThe mixture was basified by the portionwise addition of aqueous sodium hydroxide solution (10 M, 80 mL), such that the internal temperature
10. customremained below 300° C
11. customThis took 20 minutes
12. customThe dicholoromethane layer was separated
13. customevaporated nearly to dryness in vacuo
14. additionMethanol (50 mL) was added
15. customthe solvent was again removed in vacuo
16. filtrationfiltered
17. washThe filter cake was washed with methanol (20 mL)
18. customthe resulting solid dried by air suction