Cesium carbonate → HCID 86629692, compound

HRID 911698Notes

Reaction equation

HRID 911698 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]([CH3:86])([CH3:85])[CH2:75][CH2:76][C:77]1[CH:84]=[CH:83][C:80]([CH2:81][NH2:82])=[CH:79][CH:78]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[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:82][CH2:81][C:80]1[CH:83]=[CH:84][C:77]([CH2:76][CH2:75][C:74]([CH3:86])([CH3:85])[CH3:73])=[CH:78][CH:79]=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 57655914HCID 57655914, compound

Product 1

HCID 86629692HCID 86629692, compoundYield 91.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Use a method similar to the General Procedure 5-1 to react 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (623 mg, 1.46 mmol), palladium(II) acetate (33 mg, 0.146 mmol), BINAP (182 mg, 0.292 mmol), 4-(3,3-dimethyl-butyl)-benzylamine (560 mg, 2.93 mmol) and cesium carbonate (666 mg, 2.04 mmol) in degassed toluene (40 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 water. Dry the organic phase over MgSO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane and then hexane/EtOAc (19:1, 9:1) to obtain 7-chloro-6-[4-(3,3-dimethyl-butyl)-benzylamino]-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as oil (622 mg, 91%). MS (ES+) m/z: 467 (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 water
  6. dry with materialDry the organic phase over MgSO4
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customPurify the crude mixture by chromatography on silica gel eluting with hexane

Sources & evidence

ORD record
ord-b39314e0b71849778a018f43040f56ce
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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