反应详情

温度

3.799999952316284 °C

4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl trifluoromethanesulfonate 5-Hydroxy-4-methyl-3H-isobenzofuran-1-one (46.8 g, 285 mmol) was suspended in dichloromethane (935 mL) in 2-L round bottom flask equipped with overhead stirrer under nitrogen. Triethylamine (59.5 mL, 427 mmol) was added, and the reaction mixture was cooled in an ice bath to 3.8° C. Trifluoromethanesulfonic anhydride (67.4 mL, 399 mmol) was added via addition funnel over 50 min, keeping the temperature <10° C. After stirring the reaction mixture for an additional 15 min, the reaction mixture was quenched with water (200 mL), then stirred with DARCO® KB (activated carbon, 25 g) for 15 min. The biphasic mixture was filtered over SOLKA FLOC®, washing with additional dichloromethane, and transferred to a reparatory funnel, whereupon it was diluted with additional water (300 mL). The layers were separated, and the organic layer was washed with water (500 mL) and 10% brine (200 mL). The dichloromethane solution was dried over sodium sulfate, filtered and evaporated. The solid was adsorbed onto silica gel (27.5 g) and eluted through a pad of silica gel (271 g) with 25% ethyl acetatehexanes. The resulting solution was concentrated under vacuum with the product crystallizing during concentration. The suspension was filtered, the solid washed with heptane and dried under vacuum and nitrogen, providing trifluoromethanesulfonic acid 4-methyl-1-oxo-1,3-dihydro-isobenzofuran-5-yl ester. 1H NMR (400 MHz, CDCl3): δ 7.87 (d, J=8.4 Hz, 1H), 7.47 (d, J=8.4 Hz, 1H), 5.32 (s, 2H), 2.41 (s, 3H)

1. customequipped with overhead stirrer under nitrogen
2. customthe temperature <10° C
3. customthe reaction mixture was quenched with water (200 mL)
4. stirringstirred with DARCO® KB (activated carbon, 25 g) for 15 min
5. filtrationThe biphasic mixture was filtered over SOLKA FLOC®
6. washwashing with additional dichloromethane
7. customtransferred to a reparatory funnel, whereupon it
8. additionwas diluted with additional water (300 mL)
9. customThe layers were separated
10. washthe organic layer was washed with water (500 mL) and 10% brine (200 mL)
11. dry with materialThe dichloromethane solution was dried over sodium sulfate
12. filtrationfiltered
13. customevaporated
14. washeluted through a pad of silica gel (271 g) with 25% ethyl acetatehexanes
15. concentrationThe resulting solution was concentrated under vacuum with the product
16. customcrystallizing during concentration
17. filtrationThe suspension was filtered
18. washthe solid washed with heptane
19. customdried under vacuum and nitrogen