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

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Reaction Steps

Use a method similar to the General Procedure 5-2 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (300 mg, 0.71 mmol) with 1-(4-aminomethyl-3-chloro-phenyl)-3,3-dimethyl-butan-1-one (338 mg, 1.41 mmol) by using tris(dibenzylideneacetone)dipalladium(0) (130 mg, 9.142 mmol), BINAP (177 mg, 0.284 mmol) and cesium carbonate (324 mg, 0.994 mmol) in anhydrous toluene (31 mL). Purify by chromatography on silica gel eluting with hexane/EtOAc (92:8) followed by reverse phase HPLC [Hichrom Kromasil C18, 5 □M 21.2×100 mm, eluting with water/acetonitrile (0.05% TFA in each) (1:4 to 1:19 gradient over 5 min), flow rate 25 mL/min, UV detector (230 nm)] to give 7-chloro-6-[2-chloro-4-(3,3-dimethyl-butyryl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an oil (77 mg, 21%). MS (ES+) m/z: 516 (M+H)+.

Provenance & Evidence