3,4-dihydro-2H-pyran → 5-bromo-4-chloro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole

HRID 475222Notes

Reaction equation

HRID 475222 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]2[NH:6][CH:7]=[N:8][C:4]=2[C:3]=1[Cl:11].[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C1COCC1>[Br:1][C:2]1[CH:10]=[CH:9][C:5]2[N:6]([CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17][O:12]3)[CH:7]=[N:8][C:4]=2[C:3]=1[Cl:11]

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 594744835-bromo-4-chloro-1H-benzoimidazole

Product 1

HCID 712721545-bromo-4-chloro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazoleYield 90.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 128 (22 g, 0.095 mol) in dry THF (660 mL) was added 3,4-dihydro-2H-pyran (24 g, 0.286 mol) and camphorsulfonic acid (2.2 g, 0.00948 mol) and the solution was heated to reflux for 16 h. The resulting mixture was concentrated, and the residue obtained was purified by SiO2 chromatography eluting with 20% EtOAc/petroleum ether to afford 27 g (90%) of 5-bromo-4-chloro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole (130) as pale yellow solid.

Workup

  1. temperaturethe solution was heated
  2. temperatureto reflux for 16 h
  3. concentrationThe resulting mixture was concentrated
  4. customthe residue obtained
  5. customwas purified by SiO2 chromatography
  6. washeluting with 20% EtOAc/petroleum ether

Sources & evidence

ORD record
ord-be6b7e4c6dae4163833849915c796a05
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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