反应详情

温度

25 °C

Charge a nitrogen-flushed 2 L reactor that equipped with an overhead stirrer, condenser, nitrogen inlet/outlet and 500 mL addition funnel with 82.08 g (0.20 mol, 1 eq.) of 5 and 792 g (1.0 L) of acetone. Stir the slurry at 25° C. for 15 minutes. Add a solution of 34.3 mL (0.206 mol, 1.03 eq.) of 6 N hydrogen chloride in water. Add 3 mg of seed. Solids formed. Add 20 mL of water. Heat the batch to reflux (55-56° C.) and maintain at reflux for 15 minutes. Cool to 20° C. over 1.5 h. Cool to 5° C. over 1 h and filter the solids. Wash the filter cake with 80 mL of 5° C. acetone and dry the solids at 40° C., 35 mbar for 16 h to afford 70.4 g (75.7% yield) of the title compound as a yellow, crystalline solid. Following this procedure, the resulting compound is the monohydrate of the monohydrochloride salt (Polymorph Form Ha) of the Compound of Formula A.

1. additionCharge a nitrogen-
2. customflushed 2 L reactor
3. additionAdd 3 mg of seed
4. customSolids formed
5. temperatureHeat the batch
6. temperatureto reflux (55-56° C.)
7. temperaturemaintain
8. temperatureat reflux for 15 minutes
9. temperatureCool to 20° C. over 1.5 h
10. temperatureCool to 5° C. over 1 h
11. filtrationfilter the solids
12. washWash the filter cake with 80 mL of 5° C. acetone
13. customdry the solids at 40° C.