反应详情

温度

25 °C

Charge a nitrogen-flushed 3 L reactor that equipped with an overhead stirrer, condenser, nitrogen inlet/outlet and 500 mL addition funnel with 51.3 g (0.125 mol, 1 eq.) of 5 and 247 g (312 mL) of acetone. Stir the slurry at 25° C. for 15 minutes. Filter through Celite (2-5 g). Wash the reactor and filter cake with 30 g (37 mL) of acetone and combine the wash with the filtrate. Rinse the reactor with methanol and dry it with heat and vacuum. Cool the reactor and re-charge the filtrate. Warm the solution to 50° C. Add a solution of 25.7 mL (0.125 mol, 1.03 eq.) of 5 N hydrogen chloride in isopropanol and 198 g (250 mL) of acetone over 2 h. Seed after the first 5% of the acid solution has been added (about 25 mL). Maintain temperature for 15 min. Cool to 10° C. and filter the solids. Wash the filter cake with 47 g (60 mL) of acetone and dry the solids at 50° C., 35 mbar for 16 h to afford 49.4 g (88.1% yield) of 6 as a yellow, crystalline solid. Following this procedure, Compound 6 is polymorph Form A of the monohydrochloride salt of the Compound of Formula A.

1. additionCharge a nitrogen-
2. customflushed 3 L reactor
3. filtrationFilter through Celite (2-5 g)
4. washWash the reactor
5. filtrationfilter cake with 30 g (37 mL) of acetone
6. washwash with the filtrate
7. washRinse the reactor with methanol
8. customdry it
9. temperaturewith heat
10. temperatureCool the reactor
11. additionre-charge the filtrate
12. temperatureWarm the solution to 50° C
13. temperatureMaintain temperature for 15 min
14. temperatureCool to 10° C.
15. filtrationfilter the solids
16. washWash the filter cake with 47 g (60 mL) of acetone
17. customdry the solids at 50° C.