反应详情

温度

62.5 °C

1,2-Benzisoxazole-3-acetic acid (200 g; 1.13 mol) was suspended in 1,4-dioxane (600 mL). The mixture was cooled in an ice-bath and chlorosulfonic acid (82.6 mL, 1.24 mol, 1.1 eq) was added maintaining the internal temperature below 20° C. The mixture was heated to 60-65° C. for 9½ h and cooled to room-temperature. CELITE™ (20 g) was added followed by xylenes (1000 mL) and the mixture was stirred for one hour at room temperature. It was filtered and concentrated. The suspension obtained was heated to 50-60° C. for three hours and then gradually cooled to 0-5° C. and filtered. The precipitate was filtered off under a nitrogen atmosphere and washed with 400 mL 1,4-dioxane/xylenes (v/v=1:9). It was dried at 60° C. for approximately 16 hours in a vacuum oven (≦1 mm Hg) to give 218.14 g crystalline anhydrous 1,2-benzisoxazole-3-methanesulfonic acid (90.6%) with a HPLC purity of 99.4%.

1. temperatureThe mixture was cooled in an ice-bath
2. temperaturemaintaining the internal temperature below 20° C
3. temperaturecooled to room-temperature
4. additionwas added
5. filtrationIt was filtered
6. concentrationconcentrated
7. customThe suspension obtained
8. temperaturewas heated to 50-60° C. for three hours
9. temperaturegradually cooled to 0-5° C.
10. filtrationfiltered
11. filtrationThe precipitate was filtered off under a nitrogen atmosphere
12. washwashed with 400 mL 1,4-dioxane/xylenes (v/v=1:9)
13. customIt was dried at 60° C. for approximately 16 hours in a vacuum oven (≦1 mm Hg)