Cesium carbonate → HCID 87119113, compound

HRID 911669Notes

Reaction equation

HRID 911669 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.[F:73][C:74]1[CH:81]=[C:80]([F:82])[CH:79]=[CH:78][C:75]=1[CH2:76][NH2:77].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:14])([F:15])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:77][CH2:76][C:75]1[CH:78]=[CH:79][C:80]([F:82])=[CH:81][C:74]=1[F:73]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 27332442,4-DifluorobenzylamineHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 87119113HCID 87119113, compoundYield 76.1%

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 (3 g, 7.06 mmol), palladium(II) acetate (0.16 g, 0.71 mmol), BINAP (0.88 g, 1.41 mmol), 2,4-difluorobenzylamine (3.03 g, 21.18 mmol) and cesium carbonate (3.22 g, 9.88 mmol) in degassed toluene (120 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, filter through Celite® and concentrate in vacuo to give a brown oil. Purify the crude mixture by chromatography on silica gel eluting with hexane and then hexane/THF (95:5) to obtain 7-chloro-6-(2,4-difluorobenzylamino)-3-(2,2,2,trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as oil (2.25 g, 76%). MS (ES+) m/z: 419 (M+H)+.

Workup

  1. customDegas the mixture with vacuum/nitrogen
  2. custompurge
  3. temperatureCool the mixture to room temperature
  4. additiondilute with EtOAc
  5. filtrationfilter through Celite®
  6. concentrationconcentrate in vacuo
  7. customto give a brown oil
  8. customPurify the crude mixture by chromatography on silica gel eluting with hexane

Sources & evidence

ORD record
ord-c0413beb595e4323a18e5e30df13ea96
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

Loading…