反应详情

A round-bottom flask was charged with [4-(5-aminomethyl-2-fluorophenyl)-piperidine-1-yl][7-fluoro-1-(2-methoxyethyl)-4-trifluoromethoxy-1H-indol-3-yl]methanone (10.4 g, 20.4 mmol) and fumaric acid (4.74 g, 40.7 mmol). Isopropanol (IPA, 62 mL) was added and the resulting mixture was heated on a steam bath. Most of the material dissolved, before crystallization of the salt occurred. While being heated on a steam bath, additional IPA was added in 30 mL portions. Complete solution was attained after the addition of a total of 152 mL of IPA. The resulting solution was filtered and the filtrate was allowed to cool to rt. The filtrate was cooled further in an ice bath for 1.5 h, before the product was collected by filtration. The collected product was washed with cold IPA (50 mL), dried partially by suction and transferred to a drying oven where it was dried at 45° C. After drying overnight, the desired product was isolated as colorless solid: 11.8 g (84%). IR (cm−1): 3122-2700, 2920, 2824, 1698, 1584, 1512, 1443, 1397-1368, 1293-1217, 822, 794, 639. 1H NMR (300 MHz, DMSO-d6): δ 10.07 (br, 3H), 7.71 (s, 1H), 7.43 (dd, J=2.4, 7.1, 1H), 7.36 (ddd, J=2.4, 4.9, 8.4, 1H), 7.19 (d, J=8.4, 10.7, 1H), 7.10 (d, J=8.7, 11.7, 1H), 7.05 (ddd, J=1.4, 3.3, 8.7, 1H), 6.50 (s, 3H), 4.69 (br, 1H), 4.48 (t, J=5.3, 2H), 3.97 (s, 2H), 3.69 (t, J=5.4, 2H), 3.24 (s, 3H), 3.08 (dddd, J=3.5, 3.5, 12.1, 12.1, 1H), 2.91 (br, 2H), 1.75 (br, 2H), 1.63 (br, 2H). Anal. Calcd for C25H26F5N3O3-1.5C4H4O4: C, 54.31; H, 4.70; N, 6.13. Found: C, 54.30; H, 4.62; N, 6.04. MS (ESI) m/z 512.2 (M+H).

1. temperaturethe resulting mixture was heated on a steam bath
2. dissolutionMost of the material dissolved, before crystallization of the salt
3. temperatureWhile being heated on a steam bath
4. filtrationThe resulting solution was filtered
5. temperatureThe filtrate was cooled further in an ice bath for 1.5 h, before the product
6. filtrationwas collected by filtration
7. washThe collected product was washed with cold IPA (50 mL)
8. customdried partially by suction
9. customtransferred to a drying oven
10. customwhere it was dried at 45° C
11. customAfter drying overnight