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

HRID 475135Notes

Reaction equation

HRID 475135 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. The residue was diluted with water and extracted with EtOAc. The combined extracts were 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
  2. additionThe residue was diluted with water
  3. extractionextracted with EtOAc
  4. dry with materialThe combined extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by SiO2 chromatography
  8. washeluting with a DCM/MeOH gradient (0 to 9% MeOH)

Sources & evidence

ORD record
ord-9656aefd21f8430dbdbdedbee39e910c
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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