Cesium carbonate → (R)-7-chloro-6-[3-fluoro-4-(2,2,2-trifluoro-1-methyl-ethylcarbamoyl)-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 (0.561 g, 1.319 mmol) with (R)-4-aminomethyl-2-fluoro-N-(2,2,2-trifluoro-1-methyl-ethyl)-benzamide (0.698 g, 2.642 mmol) by using tris(dibenzylideneacetone)dipalladium(0) (0.241 g, 0.264 mmol), BINAP (0.33 g, 0.53 mmol) and cesium carbonate (1.51 g, 4.63 mmol) in anhydrous toluene (13 mL). Purify by chromatography on silica gel (40g RediSep® column) eluting with hexane/EtOAc (19:1 to 1:1 gradient over 30 min; 35 mL/min) and then by SCX chromatography to afford (R)-7-chloro-6-[3-fluoro-4-(2,2,2-trifluoro-1-methyl-ethylcarbamoyl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a colorless oil (0.444g, 62%). MS (ES+) m/z: 540.1 (M+H)+.

Provenance & Evidence