Cesium carbonate → 7-chloro-6-[1-(3-fluorophenyl)-ethylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Temperature

95 °C

Add palladium(II) acetate (27 mg, 0.12 mmol), BINAP (146 mg, 0.24 mmol), cesium carbonate (270 mg, 0.8 mmol) and (±)-1-(3-fluorophenyl)-ethylamine (230 mg, 1.6 mmol) to a solution of 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (250 mg, 0.6 mmol) in toluene (9 mL). Degas the slurry and fill with nitrogen. Heat the mixture to 95° C. for 16 h. Add additional palladium(II) acetate (0.1 equiv.) and BINAP (0.2 equiv.) and continue heating the reaction for an additional 24 h. Cool the mixture, dilute with EtOAc (50 mL) then filter through Celite®. Concentrate the filtrate and purify by chromatography on silica gel eluting with hexane/EtOAc (9:1 to 1:1) 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 (138 mg, 56%). GC-MS m/z: 414 (M+).

1. customDegas the slurry
2. temperaturecontinue heating
3. customthe reaction for an additional 24 h
4. temperatureCool the mixture
5. filtrationthen filter through Celite®
6. concentrationConcentrate the filtrate
7. custompurify by chromatography on silica gel eluting with hexane/EtOAc (9:1 to 1:1)

ORD record

ord-d17fe0cd79b44e518f9a47489f2f8b5b

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08022062B2