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

HRID 475108Notes

Reaction equation

HRID 475108 reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[CH:8][NH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.CC1C=CC(S(O)(=O)=O)=CC=1.O.[O:23]1[CH:28]=[CH:27][CH2:26][CH2:25][CH2:24]1>C1COCC1>[Br:1][C:2]1[C:10]2[N:9]=[CH:8][N:7]([CH:24]3[CH2:25][CH2:26][CH2:27][CH2:28][O:23]3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 112525844-Bromo-1H-benzimidazole

Product 1

HCID 712721864-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazoleYield 81.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-bromo-1H-benzo[d]imidazole (1.5 g, 7 mmol), TsOH.H2O (0.1 g, 0.7 mmol), and 3,4-dihydro-2H-pyran (2.9 g, 35 mmol) in THF (10 mL) was heated at reflux overnight. The reaction mixture was concentrated in vacuo. To the residue was added water and the mixture was extracted with EtOAc. The combined extracts were dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by SiO2 chromatography using a petroleum ether/EtOAc gradient (10:1 to 3:1) to afford 4-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole as a gray solid (1.6 g, 75%). MS (ESI): m/z=281 [M+1]+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. additionTo the residue was added water
  5. extractionthe mixture was extracted with EtOAc
  6. dry with materialThe combined extracts were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by SiO2 chromatography

Sources & evidence

ORD record
ord-c7057ce45ef742f0af41d94bca2f0746
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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