Tetrahydrofuran → HCID 71272633, compound

HRID 475232Notes

Reaction equation

HRID 475232 reaction equation
[CH3:1][C:2]1[C:3]([C:11]#[N:12])=[CH:4][C:5]2[N:9]=[CH:8][NH:7][C:6]=2[CH:10]=1.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:3]([C:11]#[N:12])=[CH:4][C:5]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:10]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 80803,4-dihydro-2H-pyranHCID 521998p-Toluenesulfonic acid monohydrateHCID 451205516-Methyl-1H-benzimidazole-5-carbonitrile

Product 1

HCID 71272633HCID 71272633, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

To a stirred solution of 6-methyl-1H-benzo[d]imidazole-5-carbonitrile (7.9 g, 50 mmol, CASRN 952511-47-6) and THF (85 mL) at RT under nitrogen was added 3,4-dihydro-2H-pyran (34 g, 0.4 mol) and p-TsOH.H2O (0.9 g, 5 mmol) and the resulting mixture was heated at 75° C. for 3 h. The reaction mixture was cooled to RT, diluted with EtOAc (200 mL), and washed sequentially with sat'd. aq. Na2CO3 (300 mL) and brine (300 mL). The organic phase was dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with a MeOH/DCM gradient (0 to 5% MeOH) to afford 7.2 g (60%) of 6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole-5-carbonitrile (176) as a yellow oil: MS (ESI) m/z=242 [M+1]+.

Workup

  1. temperatureThe reaction mixture was cooled to RT
  2. washwashed sequentially with sat'd
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by SiO2 chromatography
  7. washeluting with a MeOH/DCM gradient (0 to 5% MeOH)

Sources & evidence

ORD record
ord-500fd0184acb4d269d4960c7b3115960
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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