反应详情

Heat a stirred mixture of 6-methoxy-3-(1-piperazinyl)-1,2-benzisoxazole (0.1 mol), and 62% w/w hydrobromic acid (116.5 mL) at 115° C. under nitrogen for 6 hours. Partially concentrate under reduced pressure (15–20 mm Hg) at 50 to 60° C., add water (100 mL) and concentrate again. Repeat this process two times. Treat the residual heterogenous slurry with water (150 mL), age at 5° C. for 0.5 hour, and collect the solid by vacuum filtration. Wash the filter cake twice with cold water and dry to afford 6-hydroxy-3-(1-piperazinyl)-1,2-benzisoxazole hydrobromide (33.7 g). Suspend the crude material in water (830 mL), heat to 95–97° C., treat with activated charcoal (6.64 g), age at 95–97° C. for 0.25 hour, vacuum filter through celite, cool the filtrate to 5° C. and after 0.5 hour collect the product by vacuum filtration. Wash the filter cake twice with cold water and dry at 80° C. in high vacuum for 4 hours to afford 6-hydroxy-3-(1-piperazinyl)-1,2-benzisoxazole hydrobromide (23.5 g, 79%). The material was 99.8% pure by HPLC (Nucleosil C-18 column, 5 micron, 4.6×25 cm; mobile phase: NH4H2PO4 (0.05N):acetonitrile, 55:45 v/v; flow rate 1 mL/min; UV detection at 220/240 nm. MS (EI) 219 (M+)

1. temperatureHeat
2. concentrationPartially concentrate under reduced pressure (15–20 mm Hg) at 50 to 60° C.
3. additionadd water (100 mL)
4. concentrationconcentrate again
5. additionTreat the residual heterogenous slurry with water (150 mL), age at 5° C. for 0.5 hour
6. customcollect the solid
7. filtrationby vacuum filtration
8. washWash the filter cake twice with cold water
9. customdry