Cesium carbonate → 1-Tert-butoxycarbonyl-4-(5-fluoro-3-(2,2,2-trifluoroethyl)-2-oxo-1-benzimidazolinyl)piperidine

HRID 618379Notes

Reaction equation

HRID 618379 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3[CH:19]=[CH:20][C:21]([F:23])=[CH:22][C:17]=3[NH:16][C:15]2=[O:24])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[F:31][C:32]([F:36])([F:35])[CH2:33]I>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3[CH:19]=[CH:20][C:21]([F:23])=[CH:22][C:17]=3[N:16]([CH2:33][C:32]([F:36])([F:35])[F:31])[C:15]2=[O:24])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 677091,1,1-Trifluoro-2-iodoethane2×HCID 18695962tert-Butyl 4-(6-fluoro-1,2-dihydro-2-oxobenzo[d]imidazol-3-yl)piperidine-1-carboxylate

Product 1

HCID 186959641-Tert-butoxycarbonyl-4-(5-fluoro-3-(2,2,2-trifluoroethyl)-2-oxo-1-benzimidazolinyl)piperidine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

Solid 1-tert-butoxycarbonyl-4-(5-fluoro-2-oxo-1-benzimidazolinyl)piperidine (9.7 g, 28.9 mmol.) was dissolved in anhydrous DMF (72 mL) under an inert atmosphere and cesium carbonate (10.6 g, 32.5 mmol.) was added followed by excess 2,2,2-trifluoroethyl iodide (14.3 mL, 145 mmol.). This reaction mixture was gently warmed at 40-50° C. for an extended period (1-2 days), periodically adding additional 2,2,2-trifluoroethyl iodide (4 mL, 4 mmol in four portions) to drive the alkylation to completion. The cooled reaction mixture was diluted with EtOAc and washed with aq. NaHCO3 and water (3×). The organic layer was dried (Na2SO4) and filtered through a pad of charcoal and the solvent then evaporated. The solid residue was triturated with Et2O and collected to give 1-tert-butoxycarbonyl-4-(5-fluoro-3-(2,2,2-tri-fluoroethyl)-2-oxo-1-benzimidazolinyl)piperidine as a nearly pure white solid. This material was crystallized from CH2C2 to remove a slightly less polar impurity affording the product, mp: 172-173° C.

Workup

  1. additionwas added
  2. customThe cooled reaction mixture
  3. washwashed with aq. NaHCO3 and water (3×)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered through a pad of charcoal
  6. customthe solvent then evaporated
  7. customThe solid residue was triturated with Et2O
  8. customcollected

Sources & evidence

ORD record
ord-e0246a80659a40c4bcbb9812cb2fc776
Source dataset
uspto-grants-1999_09
Patent number
US05952351

Reaction notes

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