反应详情

A mixture of E2 free base (201.9 mg) and fumaric acid (53.9 mg) in EtOAc (2 mL) was stirred at room temperature. After 5 minutes, a milky gelatinous precipitate started to form so further EtOAc (2 mL) was added together with seed crystals of the previously obtained fumarate salt from Method 2. After 1 h, the precipitate became very thick and gelatinous so further EtOAc (2 ml) and seed crystals were added. The mixture was stirred at room temperature for 0.5 h, then warmed to 40° C. for 0.5 h. Further EtOAc (5 mL) was added and stirring was continued at 40° C. for 10 minutes then at 60° C. for 2 h. The mixture was cooled to 50° C. for ˜1 h then to 40° C. for ˜1 h then to room temperature overnight. The solid was filtered off under argon, washed with EtOAc, semi-dried under argon and then dried at 60° C. under vacuum to give the title compound (164 mg).

1. waitAfter 1 h
2. stirringThe mixture was stirred at room temperature for 0.5 h
3. temperaturewarmed to 40° C. for 0.5 h
4. stirringstirring
5. waitwas continued at 40° C. for 10 minutes
6. waitat 60° C. for 2 h
7. temperatureThe mixture was cooled to 50° C. for ˜1 h
8. waitto 40° C. for ˜1 h
9. customto room temperature
10. customovernight
11. filtrationThe solid was filtered off under argon
12. washwashed with EtOAc, semi-dried under argon
13. customdried at 60° C. under vacuum