反应详情

温度

60 °C

Alternatively, the free base of 34 was prepared as follows. A mixture of 33 (1212 g), IPA (10.8 L), (R)-3-amino-piperidine dihydrochloride (785 g), purified water (78 mL) and potassium carbonate (2.5 kg, powder, 325 mesh) was heated at 60° C. until completion (e.g., for >20 hours) as determined, for example, by HPLC. Acetonitrile (3.6 L) was then added at 60° C. and the mixture was allowed to cool to <25° C. The resultant slurry was filtered under vacuum and the filter cake was washed with acetonitrile (2×3.6 L). The filtrate was concentrated at 45° C. under vacuum (for >3 hours) to afford 2.6 kg of the free base of 34.

1. custompurified water (78 mL) and potassium carbonate (2.5 kg, powder, 325 mesh)
2. additionAcetonitrile (3.6 L) was then added at 60° C.
3. temperatureto cool to <25° C
4. filtrationThe resultant slurry was filtered under vacuum
5. washthe filter cake was washed with acetonitrile (2×3.6 L)
6. concentrationThe filtrate was concentrated at 45° C. under vacuum (for >3 hours)