3,4-dihydro-2H-pyran → 4-bromo-6-chloro-2-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole

HRID 475127Notes

Reaction equation

HRID 475127 reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[C:8]([CH3:11])[NH:7][C:6]=2[CH:5]=[C:4]([Cl:12])[CH:3]=1.CC1C=CC(S(O)(=O)=O)=CC=1.O.[O:25]1[CH:30]=[CH:29][CH2:28][CH2:27][CH2:26]1>C1COCC1>[Br:1][C:2]1[C:10]2[N:9]=[C:8]([CH3:11])[N:7]([CH:26]3[CH2:27][CH2:28][CH2:29][CH2:30][O:25]3)[C:6]=2[CH:5]=[C:4]([Cl:12])[CH:3]=1

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 532168604-Bromo-6-chloro-2-methyl-1H-benzo[d]imidazole

Product 1

HCID 712725084-bromo-6-chloro-2-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazoleYield 69.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 4-bromo-6-chloro-2-methyl-1H-benzo[d]imidazole (3.5 g, 14.26 mmol), p-TsOH.H2O (272 mg, 1.43 mmol), and 3,4-dihydro-2H-pyran (5.9 g, 71.30 mmol) in THF (20 mL) was stirred at 75° C. for 4 h. The reaction mixture was concentrated in vacuo and water was added. The mixture was extracted with EtOAc and the combined extracts dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with a DCM:MeOH gradient (0 to 9% MeOH) to afford 4-bromo-6-chloro-2-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole as a white solid (3.2 g, 69.6%). MS (ESI): m/z=329.0 [M+1]+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo and water
  2. additionwas added
  3. extractionThe mixture was extracted with EtOAc
  4. dry with materialthe combined extracts dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by SiO2 chromatography
  8. washeluting with a DCM

Sources & evidence

ORD record
ord-b174f21846b84758a673258c3b84e2d5
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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