反应详情

温度

5 °C

To a solution of the compound of Example 1I (17.28 g, 20.0 mmol, 91% chemical potency, therefore 15.72 g, 18.2 mmol) in EtOH (173 mL) at 5° C. was charged 3N KOH (33.3 mL, 100 mmol) at a rate to maintain an internal temperature <7° C. The reaction was stirred at 5° C. for 17 hour. The reaction mixture was neutralized with 3N HCl (33.3 mL, 100 mmol) while maintaining the internal temperature <10 ° C. (end pH was adjusted from 4.63 to 4.87 with 0.2 mL of 3N KOH). The reaction mixture crystallized after a few minutes post addition of 3N HCl. The reaction mixture was allowed to warm to ambient temperature, seeded (20 mg of seed crystals), warmed to 40° C. for 3 hours and slowly cooled back to ambient temperature stirred an additional 16 hours. The slurry was filtered, washed and dried to provide 14.30 g (92.4%) of the title compound.

1. temperatureto maintain an internal temperature <7° C
2. customThe reaction mixture crystallized after a few minutes post addition of 3N HCl
3. temperatureto warm to ambient temperature
4. temperaturewarmed to 40° C. for 3 hours
5. temperatureslowly cooled back to ambient temperature
6. stirringstirred an additional 16 hours
7. filtrationThe slurry was filtered
8. washwashed
9. customdried