Tetrahydrofuran → 4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole-5-carbonitrile

HRID 475243Notes

Reaction equation

HRID 475243 reaction equation
[CH3:1][C:2]1[C:10]2[N:9]=[CH:8][NH:7][C:6]=2[CH:5]=[CH:4][C:3]=1[C:11]#[N:12].C1COCC1.[O:18]1[CH:23]=[CH:22][CH2:21][CH2:20][CH2:19]1.CC1C=CC(S(O)(=O)=O)=CC=1.O>CCOC(C)=O>[CH3:1][C:2]1[C:10]2[N:9]=[CH:8][N:7]([CH:19]3[CH2:20][CH2:21][CH2:22][CH2:23][O:18]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[C:11]#[N:12]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 451205504-methyl-1H-benzimidazole-5-carbonitrile

Product 1

HCID 712725774-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole-5-carbonitrileYield 77.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 160 (8.3 g, 52.5 mmol) and THF (100 mL) at RT under nitrogen was added, 3,4-dihydro-2H-pyran (35 g, 420 mmol) and p-TsOH.H2O (0.9 g, 5.3 mmol) and the reaction mixture was heated at 75° C. for 4 h. The mixture was cooled to RT, diluted with EtOAc and sequentially washed with sat'd. aq. NaHCO3, and brine. The organic extract was dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with a MeOH/DCM gradient (0 to 5% MeOH) to afford 9.8 g (77%) of 4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole-5-carbonitrile (162) as a light yellow solid: MS (ESI) m/z=242 [M+1]+.

Workup

  1. washsequentially washed with sat'd
  2. extractionThe organic extract
  3. dry with materialwas dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by SiO2 chromatography
  7. washeluting with a MeOH/DCM gradient (0 to 5% MeOH)

Sources & evidence

ORD record
ord-943b9a591bef4c7f84b74cb01e7613f5
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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