反应详情

温度

80 °C

(1S,5S)-3-(5,6-dichloropyridin-3-yl)-3,6-diazabicyclo[3.2.0]heptane benzenesulfonate (250 g) was suspended in methylene chloride (1000 mL). 20% aqueous potassium hydroxide (700 mL) was added and, after mixing and settling, the layers were separated. The organic layer was washed two more times with 700 mL 20% aqueous potassium hydroxide, followed by a 700 mL water wash. The combined organic layers were dried over sodium sulfate and then concentrated to an oil. The residue was dissolved in isopropyl acetate (1000 mL) and concentrated to a solid. The residue was then suspended in isopropyl acetate (1000 mL) and heated to 80° C. to dissolve everything. Insolubles were removed by filtration. The solution was cooled to room temperature, with rapid stirring. The resulting slurry was concentrated further by distillation of approximately 250 mL isopropyl acetate. After cooling in the refrigerator for 3 hours (˜5° C.), the product was isolated by filtration. The wetcake was washed with isopropyl acetate and then dried in a vacuum oven at 50° C. An off-white solid was obtained (109.6 g).

1. additionafter mixing
2. customthe layers were separated
3. washThe organic layer was washed two more times with 700 mL 20% aqueous potassium hydroxide
4. washwash
5. dry with materialThe combined organic layers were dried over sodium sulfate
6. concentrationconcentrated to an oil
7. dissolutionThe residue was dissolved in isopropyl acetate (1000 mL)
8. concentrationconcentrated to a solid
9. dissolutionto dissolve everything
10. customInsolubles were removed by filtration
11. temperatureThe solution was cooled to room temperature, with rapid stirring
12. concentrationThe resulting slurry was concentrated further by distillation of approximately 250 mL isopropyl acetate
13. temperatureAfter cooling in the refrigerator for 3 hours (˜5° C.)
14. customthe product was isolated by filtration
15. washThe wetcake was washed with isopropyl acetate
16. customdried in a vacuum oven at 50° C
17. customAn off-white solid was obtained (109.6 g)