Cesium carbonate → HCID 86629676, compound

HRID 911677Notes

Reaction equation

HRID 911677 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.[CH:73]1([C:79]([C:81]2[CH:88]=[CH:87][C:84]([CH2:85][NH2:86])=[CH:83][CH:82]=2)=[O:80])[CH2:78][CH2:77][CH2:76][CH2:75][CH2:74]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=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.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:86][CH2:85][C:84]1[CH:87]=[CH:88][C:81]([C:79]([CH:73]2[CH2:78][CH2:77][CH2:76][CH2:75][CH2:74]2)=[O:80])=[CH:82][CH:83]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 28343697HCID 28343697, compoundHCID 574477477-Chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethylsulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 86629676HCID 86629676, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Use a method similar to the General Procedure 5-2 to react 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (150 mg, 0.353 mmol), tris(dibenzylideneacetone)dipalladium(0) (64 mg, 0.071 mmol), BINAP (88 mg, 0.141 mmol), 4-cyclohexanecarbonyl-benzylamine (125 mg, 0.576 mmol) and cesium carbonate (230 mg, 0.706 mmol) in degassed toluene (10 mL). Degas the mixture with vacuum/nitrogen purge and heat to 100° C. for 6 h. Cool the mixture to room temperature, dilute with EtOAc and filter through Celite®. Purify the crude mixture by chromatography on silica gel eluting with hexane and then hexane/EtOAc (90:10 and 85:15) to obtain 7-chloro-6-(4-cyclohexanecarbonyl-benzylamino)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as oil (130 mg, 75%). MS (ES+) m/z: 493 (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. customPurify the crude mixture by chromatography on silica gel eluting with hexane

Sources & evidence

ORD record
ord-e7b2841a10df4d67ac0338bf9beefff3
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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