3,4-dihydro-2H-pyran → 5-bromo-7-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole

HRID 475199Notes

Reaction equation

HRID 475199 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]([CH3:11])[C:5]2[NH:6][CH:7]=[N:8][C:4]=2[CH:3]=1.CC1C=CC(S(O)(=O)=O)=CC=1.O.[O:24]1[CH:29]=[CH:28][CH2:27][CH2:26][CH2:25]1>C1COCC1>[Br:1][C:2]1[CH:10]=[C:9]([CH3:11])[C:5]2[N:6]([CH:25]3[CH2:26][CH2:27][CH2:28][CH2:29][O:24]3)[CH:7]=[N:8][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 178422430HCID 178422430, compound

Product 1

HCID 712721595-bromo-7-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazoleYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 74 (1.09 g, 5.19 mmol), TsOH.H2O (98 mg, 0.51 mmol), 3,4-dihydro-2H-pyran (2.4 mL, 26 mmol) in THF (15 mL) was degassed and then heated to reflux overnight. The solvent was removed in vacuo. The residue was partitioned between with DCM (300 mL) and water (50 mL). The organic layer was separated, dried (MgSO4), filtered and concentrated. The crude product was purified by SiO2 chromatography eluting with a MeOH/DCM gradient (0.5% to 1% MeOH) to afford 1.45 g (95%) of 5-bromo-7-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole (76) as yellow solid: MS (ESI) m/z=295.1 [M+1]+.

Workup

  1. customwas degassed
  2. temperatureheated
  3. temperatureto reflux overnight
  4. customThe solvent was removed in vacuo
  5. customThe residue was partitioned between with DCM (300 mL) and water (50 mL)
  6. customThe organic layer was separated
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by SiO2 chromatography
  11. washeluting with a MeOH/DCM gradient (0.5% to 1% MeOH)

Sources & evidence

ORD record
ord-b427b8fd3a9648289ed49b788c49cc2d
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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