Butyl vinyl ether → 1-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)ethanone

HRID 475202Notes

Reaction equation

HRID 475202 reaction equation
Br[C:2]1[CH:16]=[CH:15][C:5]2[N:6]([CH:9]3[CH2:14][CH2:13][CH2:12][CH2:11][O:10]3)[CH:7]=[N:8][C:4]=2[CH:3]=1.[CH:17]([O:19]CCCC)=[CH2:18].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>Cl[Pd]Cl.CC(O)C>[O:10]1[CH2:11][CH2:12][CH2:13][CH2:14][CH:9]1[N:6]1[C:5]2[CH:15]=[CH:16][C:2]([C:17](=[O:19])[CH3:18])=[CH:3][C:4]=2[N:8]=[CH:7]1

Participants

6

Reactant 3

HCID 8108Butyl vinyl etherHCID 62657Potassium Phosphate, TribasicHCID 672932855-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole

Product 1

HCID 712726001-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)ethanoneYield 86%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 3776IsopropanolSolvent

Procedure

A mixture of 80 (2.81 g, 0.01 mol), butyl vinyl ether (1.5 g, 0.015 mol), PdCl2 (26 mg, 0.14 mmol), (o-tolyl)3P (88 mg, 0.29 mmol), K3PO4 (1.5 g, 0.02 mol), and IPA (20 ml) was heated at reflux under nitrogen overnight. The mixture was cooled to RT and the solvent was removed in vacuo. To the residue was added 6M HCl (60 mL) and the resulting solution stirred for 15 min. The mixture was adjusted to pH 8 with aqueous NH4OH (35%) and was extracted with EtOAc (300 mL). The organic layer was washed with brine (50 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with a DCM/MeOH gradient (5 to 10% MeOH) to afford 1.2 g (86%) of 1-(1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)ethanone (82) as yellow oil: MS (ESI) m/z=245.3 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux under nitrogen overnight
  3. customthe solvent was removed in vacuo
  4. additionTo the residue was added 6M HCl (60 mL)
  5. extractionwas extracted with EtOAc (300 mL)
  6. washThe organic layer was washed with brine (50 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by SiO2 chromatography
  11. washeluting with a DCM/MeOH gradient (5 to 10% MeOH)

Sources & evidence

ORD record
ord-819f4c5d6b96476686065ed354039ee7
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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