Cesium carbonate → 4-[4-Fluoro-3-(1-methyl-1H-benzoimidazol-2-yl)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 2047391Notes

Reaction equation

HRID 2047391 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C:8]2[N:12]([CH3:13])[C:11]3[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=3[N:9]=2)[CH:7]=1.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].C(=O)([O-])[O-].[Cs+].[Cs+]>CCOC(C)=O.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]>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][N:29]([C:2]2[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C:8]3[N:12]([CH3:13])[C:11]4[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=4[N:9]=3)[CH:7]=2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 595681902-(5-Bromo-2-fluoro-phenyl)-1-methyl-1H-benzoimidazole

Product 1

HCID 686709934-[4-Fluoro-3-(1-methyl-1H-benzoimidazol-2-yl)-phenyl]-piperazine-1-carboxylic acid tert-butyl esterYield 54%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

2-(5-Bromo-2-fluoro-phenyl)-1-methyl-1H-benzoimidazole (2.10 g, 6.9 mmol), piperazine-1-carboxylic acid tert-butyl ester (1.16 g, 8.3 mmol), cesium carbonate (3.14 g, 9.6 mmol) rac-2,2′ bis(diphenylphosphino)-1,1′-binaphtyl (BINAP) (0.17 g, 0.28 mmol) and tris-(dibenzilideneacetone)dipalladium(0) (0.06 g, 0.07 mmol) were placed in a Schlenk tube and purged by repeated nitrogen/vacuum cycles for 10 minutes. Dry toluene (13 mL) was added and the reaction was stirred at 85° C. for 24 h. Reaction was cooled to room temperature, diluted with AcOEt (20 mL) and washed with water (10 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude reaction mixture was purified by flash chromatography (eluent: cyclohexane:AcOEt gradient from 100% cyclohexane to cyclohexane 2:AcOEt 1) to afford 1.14 g of the starting material and 0.70 g of the title compound (54%).

Workup

  1. custompurged by repeated nitrogen/vacuum cycles for 10 minutes
  2. additionDry toluene (13 mL) was added
  3. customReaction
  4. temperaturewas cooled to room temperature
  5. washwashed with water (10 mL)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe crude reaction mixture
  9. customwas purified by flash chromatography (eluent: cyclohexane:AcOEt gradient from 100% cyclohexane to cyclohexane 2:AcOEt 1)

Sources & evidence

ORD record
ord-509dbae7c3dc4547b0d7643f74f84d23
Source dataset
uspto-grants-2013_11
Patent number
US08592463B2

Reaction notes

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