3,4-dihydro-2H-pyran → 5-bromo-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole

HRID 475212Notes

Reaction equation

HRID 475212 reaction equation
[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:5]2[NH:6][CH:7]=[N:8][C:4]=2[CH:3]=1.[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1>C1COCC1.CC1C=CC(S(O)(=O)=O)=CC=1.O>[Br:1][C:2]1[C:10]([F:11])=[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[CH:3]=1

Participants

5

Reactant 2

HCID 80803,4-dihydro-2H-pyranHCID 532169315-Bromo-6-fluoro-1H-benzo(d)imidazole

Product 1

HCID 712723505-bromo-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazoleYield 106.3%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 100 (550 mg, 2.57 mmol), TsOH.H2O (50 mg, 0.26 mmol), and 3,4-dihydro-2H-pyran (1.08 g, 12.85 mmol) in THF (10 mL) was heated at reflux overnight. After the solvent was removed in vacuo, the residue was partitioned between DCM (300 mL) and water (100 mL). The organic layer was separated, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with a MeOH/DCM gradient (0.5 to 1% MeOH) to afford 817 mg (100%) of 5-bromo-6-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole (102) as yellow oil: MS (ESI) m/z=299 [M+1]+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. customAfter the solvent was removed in vacuo
  4. customthe residue was partitioned between DCM (300 mL) and water (100 mL)
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by SiO2 chromatography
  10. washeluting with a MeOH/DCM gradient (0.5 to 1% MeOH)

Sources & evidence

ORD record
ord-76faaf8a3d014dfa823a5b027315005c
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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