Cesium carbonate → 2,3,4,5-Tetrahydro-1H-benzo(d)azepine

HRID 1191157Notes

Reaction equation

HRID 1191157 reaction equation
Cl[C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8](C(=O)C(F)(F)F)[CH2:9][CH2:10][C:4]=2[C:3]=1OS(C(F)(F)F)(=O)=O.CC(C)(C)CC(C1SC(C2C=CC(CN)=CC=2)=CC=1)=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+]>C1(C)C=CC=CC=1.CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:10]1[C:4]2[CH:3]=[CH:2][CH:18]=[CH:17][C:5]=2[CH2:6][CH2:7][NH:8][CH2:9]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 58495498HCID 58495498, compound

Product 1

HCID 14002432,3,4,5-Tetrahydro-1H-benzo(d)azepineYield 261.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 21735183Dimethylformamide tolueneSolvent

Procedure

Use a method similar to the General Procedure 1-2 to couple 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (93.5 mg, 0.2 mmol) with 4-[5-(3,3-dimethylbutyryl)tiophen-2-yl]-benzylamine (129 mg, 0.4 mmol) using tris(dibenzylideneacetone)dipalladium(0) (40.3 mg, 0.04 mmol), BINAP (58.3 mg, 0.08 mmol) and cesium carbonate (100 mg, 0.3 mmol) in toluene/DMF (11:1, 12 mL). Purify by chromatography on silica gel eluting with hexane/EtOAc (4:1) to give 7-chloro-6-{4-[5-(3,3-dimethylbutyryl)-tiophen-2-yl]-benzylamino}trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a yellow oil (77 mg, 62%). MS (ES+) m/z: 563 (M+H)+.

Workup

  1. customPurify by chromatography on silica gel eluting with hexane/EtOAc (4:1)

Sources & evidence

ORD record
ord-3ced42253266425988aff822fd7eaee3
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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