Dimethylformamide → (1-(ethoxycarbonylmethyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine

HRID 323490Notes

Reaction equation

HRID 323490 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.CN(C)C=O.[H-].[Na+].Br[CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34]>CO.ClCCl>[CH2:36]([O:35][C:33]([CH2:32][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)=[O:34])[CH3:37]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 22036999tert-Butyl 4-((1H-benzo[d]imidazol-2-yl)amino)piperidine-1-carboxylate

Product 1

HCID 22009058(1-(ethoxycarbonylmethyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

Combine (1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine (0.5 g, 1.58 mmol) and dimethylformamide (10 mL). Add portionwise, sodium hydride (0.08 g, 60% in oil, 1.66 mmol). After 30 minutes, add ethyl bromoacetate (0.277 g, 1.66 mmol). After 12 hours, quench by the addition of water and extract the quenched reaction mixture with dichloromethane. Separate the layers and extract the organic layer with five times with water. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 5% methanol/dichloromethane to give (1-(ethoxycarbonylmethyl)-1H-benzimidazol-2-yl)(1-(t-butoxycarbonyl)piperidin-4-yl)amine.

Workup

  1. additionAdd portionwise
  2. waitAfter 12 hours
  3. customquench by the addition of water
  4. extractionextract
  5. customthe quenched reaction mixture with dichloromethane
  6. customSeparate the layers
  7. extractionextract the organic layer with five times with water
  8. dry with materialDry the organic layer over Na2SO4
  9. filtrationfilter
  10. customevaporate in vacuo
  11. customto give a residue

Sources & evidence

ORD record
ord-f8b7fed7d0ed499c9efcd99fc256ff8d
Source dataset
uspto-grants-2001_04
Patent number
US06211199B1

Reaction notes

Loading…