反应详情

温度

100 °C

To Compound 8 (100 g, 0.204 mol, 1.00 eq) was added a 7M sulfuric acid solution prepared by the slow addition of concentrated sulfuric acid (285 mL, 2.85 vol, 5.24 mol) to distilled water (465 mL, 4.65 vol) while keeping the temperature below 50° C. The mixture was heated at 100±5° C. until the reaction was complete. The mixture was then cooled to 30±5° C. and additional water (750 mL, 7.5 vol) was added. Isopropyl acetate (2 L, 20 vol) was then added and the mixture was stirred for 15 minutes. Stirring was stopped and the phases were allowed to separate. The aqueous phase was separated and water (7.5 vol) was charged to the organic phase. The mixture was stirred for 15 minutes, polish filtered, then the aqueous phase was drained. The total volume of the organic layer was reduced to 4 vol by vacuum distillation at 45±5° C. The resulting slurry was cooled to −10° C. for 12 hours and filtered. The filter and cake was washed with cold isopropyl acetate (3 vol) and the solids were dried under vacuum at 50±5° C. to give the title Compound, 9, as a white solid. (1H NMR, 500 MHz; DMSO-d6) δ 12.50 (s, 1H), 9.25 (s, 1H), 8.07 (d, 1H), 7.39 (q, 1H), 7.29 (m, 1H), 7.18 (m, 3H), 7.09 (m, 1H), 6.25 (m, 1H).

1. distillationto distilled water (465 mL, 4.65 vol)
2. customthe temperature below 50° C
3. temperatureThe mixture was then cooled to 30±5° C.
4. additionadditional water (750 mL, 7.5 vol) was added
5. additionIsopropyl acetate (2 L, 20 vol) was then added
6. stirringStirring
7. customto separate
8. customThe aqueous phase was separated
9. additionwater (7.5 vol) was charged to the organic phase
10. stirringThe mixture was stirred for 15 minutes
11. filtrationpolish filtered
12. distillationThe total volume of the organic layer was reduced to 4 vol by vacuum distillation at 45±5° C
13. temperatureThe resulting slurry was cooled to −10° C. for 12 hours
14. filtrationfiltered
15. filtrationThe filter
16. washcake was washed with cold isopropyl acetate (3 vol)
17. customthe solids were dried under vacuum at 50±5° C.