反应详情

温度

67 °C

[1-(5-Chloro-2,3-dimethoxy-phenyl)-ethyl]-(5-fluoro-2-methanesulfonyl-phenyl)-amine (100 g, 0.26 mol), piperazine (444 g, 5.16 mol), Hunig's base (0.45 L, 2.6 mol) and ACN (0.75 L) were heated at 80° C. for 13.5 hours (a solution formed upon heating to 67° C.). Upon cooling, a large amount of solids precipitated. Filtration, washing of the filter cake with ACN, and concentration afforded a solid which was treated with 1 L EtOAc. The EtOAc layers were combined and washed with 3×1 L water, dried over sodium sulfate, and concentrated to give 26 g of product. The solid collected by filtration was suspended in 0.5 L DCM and washed with 0.5 L water. The water was back-extracted with 0.25 L DCM. The DCM layers were combined, washed with 7×0.5 L water, dried over sodium sulfate and concentrated. 65 g of the resulting white solid were suspended in TBME and left o/n. The mixture was filtered, re-triturated in 210 mL TBME, filtered, washed with 70 mL TBME and air-dried to afford 59.4 g (50.7%) of product as a white solid.

1. customformed
2. temperatureUpon cooling
3. customa large amount of solids precipitated
4. filtrationFiltration
5. washwashing of the filter cake with ACN, and concentration
6. customafforded a solid which
7. washwashed with 3×1 L water
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated