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

HRID 2041559Notes

Reaction equation

[CH3:1][CH:2]([CH2:12][CH3:13])[CH2:3][C:4]1[CH:11]=[CH:10][C:7]([CH2:8][NH2:9])=[CH:6][CH:5]=1.[Cl:14][C:15]1[CH:31]=[CH:30][C:18]2[CH2:19][CH2:20][N:21]([C:24](=[O:29])[C:25]([F:28])([F:27])[F:26])[CH2:22][CH2:23][C:17]=2[C:16]=1OS(C(F)(F)F)(=O)=O.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[Cl:14][C:15]1[CH:31]=[CH:30][C:18]2[CH2:19][CH2:20][N:21]([C:24](=[O:29])[C:25]([F:26])([F:28])[F:27])[CH2:22][CH2:23][C:17]=2[C:16]=1[NH:9][CH2:8][C:7]1[CH:6]=[CH:5][C:4]([CH2:3][CH:2]([CH3:1])[CH2:12][CH3:13])=[CH:11][CH:10]=1

Participants

Conditions

Temperature: 95 °C

Procedure

Under a nitrogen atmosphere, add 4-(2-methyl-butyl)-benzylamine (450 mg, 2.54 mmol), 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (720 mg, 1.7 mmol), palladium(II) acetate (40 mg, 0.17 mmol), BINAP (222 mg, 0.34 mmol) and cesium carbonate (1.4 g, 4.3 mmol) to toluene (20 mL). Heat the mixture at 95° C. for 12 h. Cool the mixture to room temperature and apply the mixture to a silica gel column eluting with hexane/EtOAc (10:1) to provide 7-chloro-6-[4-(2-methyl-butyl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (450 mg, 59%). MS (ES+) m/z: 453 (M+H)+.

Workup

temperatureCool the mixture to room temperature
washapply the mixture to a silica gel column eluting with hexane/EtOAc (10:1)

Sources & evidence

ORD record: ord-af23f83ebcf34e6bbc02342f8467af57
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580780B2

Reaction notes

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