反应详情

温度

70 °C

Crude (2S)-2-[(benzylamino)methyl]-2,3,8,9-tetrahydro-7H-[1,4]dioxino[2,3-e]indol-8-one (0.85 g, 2.7 mmol) is dissolved in EtOH (18 mL) and heated to 70° C. Solid fumaric acid (0.31 g, 2.7 mmol) is added in one portion to the hot solution, and the heat is turned off. Once the solution is at 55° C., seed crystals are introduced and the mixture is allowed to continue cooling to rt over 1.5 h. The slurry is further cooled to 5° C. by immersion in an ice water bath held at this temperature for 30 min and collected by vacuum filtration. The filter cake is washed with cold EtOH (10 mL) and dried under suction giving the title compound (0.70 g, 62%) as a pink powder. LCMS (Basic Method): 1.84 min, 311 (M+H)+. 1H NMR (300 MHz, DMSO-d6) δ 10.17 s, 1H), 7.38-7.21 (m, 5H), 6.66 (d, J=8.2 Hz, 1H), 6.57 (s, 2H), 6.28 (d, J=8.2 Hz, 1H), 4.35-4.33 (m, 1H), 4.25 (dd, J=2.2, 11.7 Hz, 1H), 3.96 (dd, J=6.4, 11.5 Hz, 1H), 3.83 (s, 2H), 3.32 (s, 2H), 2.83-2.81 (m, 2H), NH, and two OH's not observed.

1. customis at 55° C.
2. additionseed crystals are introduced
3. temperatureto continue cooling to rt over 1.5 h
4. temperatureThe slurry is further cooled to 5° C. by immersion in an ice water bath
5. filtrationcollected by vacuum filtration
6. washThe filter cake is washed with cold EtOH (10 mL)
7. customdried under suction