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

HRID 911672Notes

Reaction equation

HRID 911672 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=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.[CH3:73][C:74]([CH3:87])([CH3:86])[CH2:75][C:76]([C:78]1[CH:85]=[CH:84][C:81]([CH2:82][NH2:83])=[CH:80][CH:79]=1)=[O:77].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=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]>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:83][CH2:82][C:81]1[CH:84]=[CH:85][C:78]([C:76](=[O:77])[CH2:75][C:74]([CH3:86])([CH3:73])[CH3:87])=[CH:79][CH:80]=1

Participants

8

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 576563504-(3,3-Dimethyl-butyryl)-benzylamine

Product 1

HCID 866296717-chloro-6-[4-(3,3-dimethyl-butyryl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 65.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Use a method similar to the General Procedure 5-3 to react 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (250 mg, 0.588 mmol), palladium(II) acetate (26 mg, 0.118 mmol), tris(dibenzylideneacetone)dipalladium(0) (53 mg, 0.059 mmol), BINAP (0.22 g, 0.353 mmol), 4-(3,3-dimethyl-butyryl)-benzylamine (241 mg, 1.176 mmol) and cesium carbonate (383 mg, 1.176 mmol) in degassed toluene (10 mL). Degas the mixture with vacuum/nitrogen purge and heat to 100° C. for 16 h. Cool the mixture to room temperature, dilute with EtOAc and wash with saturated aqueous NaHCO3. Dry the organic layer over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane and then hexane/EtOAc (90:10, 85:15) to obtain 7-chloro-6-[4-(3,3-dimethyl-butyryl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as oil (185 mg, 65%). MS (ES+) m/z: 481 (M+H)+.

Workup

  1. customDegas the mixture with vacuum/nitrogen
  2. custompurge
  3. temperatureCool the mixture to room temperature
  4. additiondilute with EtOAc
  5. washwash with saturated aqueous NaHCO3
  6. dry with materialDry the organic layer over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customPurify the crude mixture by chromatography on silica gel eluting with hexane

Sources & evidence

ORD record
ord-82f079ac97b44800982ba09f6bbce7c8
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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