反应详情

温度

95 °C

Add tris(dibenzylideneacetone)dipalladium(0) (3.4 g, 3.8 mmol), BINAP (4.7 g, 7.5 mmol), cesium carbonate (8.6 g, 26.3 mmol) and 1-(3-fluorophenyl)-ethylamine Isomer 2 (5.8 g, 41.3 mmol) to a solution of 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (8.0 g, 18.8 mmol) in toluene (225 mL). Degas the slurry and fill with nitrogen. Heat the mixture to 95° C. for 8 h. Add additional tris(dibenzylideneacetone)dipalladium(0) (0.1 equiv.), and BINAP (0.2 equiv.). Continue heating the reaction for an additional 16 h. Cool the mixture, dilute with EtOAc (200 mL) then filter thru Celite®. Concentrate in vacuo and purify by chromatography on silica gel eluting with hexane/EtOAc (9:1) followed by SCX chromatography to obtain 7-chloro-6-[1-(3-fluorophenyl)-ethylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (6.0 g, 78%). GC-MS m/z: 414 (M+).

1. customDegas the slurry
2. temperatureContinue heating
3. customthe reaction for an additional 16 h
4. temperatureCool the mixture
5. filtrationthen filter
6. concentrationConcentrate in vacuo
7. custompurify by chromatography on silica gel eluting with hexane/EtOAc (9:1)