Sodium Iodide → (1-(2-(trifluoromethoxy)ethyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine

HRID 323512Notes

Reaction equation

HRID 323512 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1.[H-].[Na+].[F:26][C:27]([F:38])([F:37])[O:28]OCCOS(C)(=O)=O.[I-].[Na+].[C:41](OCC)(=O)[CH3:42]>CN(C)C=O.C(OCC)(=O)C.CCCCCC.CCCCCC>[F:38][C:27]([F:26])([F:37])[O:28][CH2:41][CH2:42][N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1

Participants

9

Reactant 5

HCID 5238Sodium IodideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 184645582-(Methanesulfonyloxy)ethyl trifluoromethoxy etherHCID 22036999tert-Butyl 4-((1H-benzo[d]imidazol-2-yl)amino)piperidine-1-carboxylate

Product 1

HCID 22009444(1-(2-(trifluoromethoxy)ethyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8058HexaneSolventHCID 21226206Ethyl acetate hexaneSolvent2×

Procedure

Combine (1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine (0.158 g, 0.5 mmol) and dimethylformamide (4 mL). Cool in an ice-bath. Add sodium hydride (0.013 g, 60% in oil, 55 mmol). Warm to ambient temperature. After 30 minutes, add a solution of 2-(methanesulfonyloxy)ethyl trifluoromethoxy ether (0.15 g, 0.75 mmol) in dimethylformamide (1 mL). Add sodium iodide (0.11 g, 075 mmol). After 2 hours, heat to 80° C. After 4 hours, cool to ambient temperature. After 18 hours dilute the reaction mixture with ethyl acetate and extract with brine. Dry the organic layer over MgSO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with hexane, 30% ethyl acetate/hexane and then 50% ethyl acetate/hexane to give (1-(2-(trifluoromethoxy)ethyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine: Rf=0.26 (silica gel, 50% ethyl acetate/hexane).

Workup

  1. temperatureCool in an ice-bath
  2. waitAfter 2 hours
  3. temperatureheat to 80° C
  4. waitAfter 4 hours
  5. temperaturecool to ambient temperature
  6. extractionextract with brine
  7. dry with materialDry the organic layer over MgSO4
  8. filtrationfilter
  9. customevaporate in vacuo
  10. customto give a residue

Sources & evidence

ORD record
ord-ce25223739a24a39b52cba26dda738dd
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

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