Cesium carbonate → HCID 68671838, compound

HRID 2047394Notes

Reaction equation

HRID 2047394 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[C:17]1[CH:22]=[C:21](Br)[CH:20]=[CH:19][C:18]=1[F:24])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].C(=O)([O-])[O-].[Cs+].[Cs+].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)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[C:17]1[CH:22]=[C:21]([N:35]2[CH2:34][CH2:33][N:32]([C:30]([O:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:31])[CH2:37][CH2:36]2)[CH:20]=[CH:19][C:18]=1[F:24])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-2×HCID 68670860HCID 68670860, compound

Product 1

HCID 68671838HCID 68671838, compoundYield 76.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 1140TolueneSolvent2×

Conditions

Temperature
85 °C

Procedure

2-(5-Bromo-2-fluoro-phenyl)-benzoimidazole-1-carboxylic acid tert-butyl ester (2.52 g, 6.5 mmol), piperazine-1-carboxylic acid tert-butyl ester (1.56 g, 8.40 mmol) and cesium carbonate (10.50 g, 32.20 mmol) were placed into a dry 500 mL round bottom flask under nitrogen and dry toluene (140 mL) was added. At the same time palladium acetate (0.29 g, 1.30 mmol) and BINAP (1.20 g, 1.93 mmol) were placed into a dry 250 mL round bottom flask under nitrogen and dry toluene (140 mL) was added. After 10 minutes the suspension containing BINAP and Palladium acetate was added to the 500 mL round bottom flask. The reaction mixture was heated at 85° C. overnight under nitrogen and cooled to room temperature. The mixture was filtered and the insoluble material was washed with EtOAC (3×20 mL). The organic solution was concentrated under reduced pressure and crude was purified by flash chromatography (eluent: cyclohexane:AcOEt gradient from 100% of cyclohexane to cyclohexane 4:AcOEt 1) to afford 2.48 g of the title compound (76%).

Workup

  1. additionwas added to the 500 mL round bottom flask
  2. temperaturecooled to room temperature
  3. filtrationThe mixture was filtered
  4. washthe insoluble material was washed with EtOAC (3×20 mL)
  5. concentrationThe organic solution was concentrated under reduced pressure and crude
  6. customwas purified by flash chromatography (eluent: cyclohexane:AcOEt gradient from 100% of cyclohexane to cyclohexane 4:AcOEt 1)

Sources & evidence

ORD record
ord-d3c1f7b7b76f431ea20f7b6fa86452bc
Source dataset
uspto-grants-2013_11
Patent number
US08592463B2

Reaction notes

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