3,4-dihydro-2H-pyran → methyl 1-(tetrahydro-2H-pyran-2-yl)-1H-benzimidazole-5-carboxylate

HRID 475172Notes

Reaction equation

HRID 475172 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]([O:12][CH3:13])=[O:11])=[CH:9][C:4]=2[N:3]=[CH:2]1.[O:14]1[CH:19]=[CH:18][CH2:17][CH2:16][CH2:15]1>CC1C=CC(S(O)(=O)=O)=CC=1.O.C1COCC1>[O:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH:15]1[N:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]([O:12][CH3:13])=[O:11])=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

5

Reactant 2

HCID 80803,4-dihydro-2H-pyranHCID 178497374HCID 178497374, compound

Product 1

HCID 58324962methyl 1-(tetrahydro-2H-pyran-2-yl)-1H-benzimidazole-5-carboxylateYield 96%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A round-bottom flask was charged with 20 (1.76 g, 10 mmol), p-TsOH.H2O (38 mg, 0.2 mmol), 3,4-dihydro-2H-pyran (1.26 g, 15 mmol) and THF (20 mL). The reaction mixture was degassed with nitrogen and heated at reflux for 18 h, and then the solvent was removed under reduced pressure. The residue was diluted with DCM (250 mL) and water (50 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with a DCM/MeOH gradient (0.5 to 1.0% MeOH) to afford 2.5 g (90%) of methyl 1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole-5-carboxylate (22) as a grey oil: MS (ESI) m/z=261.2 [M+1]+.

Workup

  1. customThe reaction mixture was degassed with nitrogen
  2. temperatureheated
  3. temperatureat reflux for 18 h
  4. customthe solvent was removed under reduced pressure
  5. additionThe residue was diluted with DCM (250 mL) and water (50 mL)
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by SiO2 chromatography
  10. washeluting with a DCM/MeOH gradient (0.5 to 1.0% MeOH)

Sources & evidence

ORD record
ord-bc753d52187c427eb2bf0da212da4ee9
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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