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

HRID 475279Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 5-bromo-4-methyl-1H-benzo[d]imidazole (1.0 g, 4.74 mmol, CASRN 952511-48-7) and 3,4-dihydro-2H-pyran (2.0 g, 23.70 mmol) in THF (10 mL) was added p-TsOH.H2O (90 mg, 0.47 mmol). The mixture was heated at 80° C. overnight, cooled and the solvent was removed in vacuo. The residue was diluted with DCM (100 mL) and water (50 mL). The organic layer was separated, dried (MgSO4), filtered and concentrated to dryness in vacuo. The crude product was purified by SiO2 chromatography eluting with a petroleum ether/EtOAc gradient (10 to 50% EtOAc) to afford 800 mg (57%) of 5-bromo-4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole (254) as light yellow solid: MS (ESI) m/z=295.1 [M+1]+.

Workup

temperaturecooled
customthe solvent was removed in vacuo
additionThe residue was diluted with DCM (100 mL) and water (50 mL)
customThe organic layer was separated
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated to dryness in vacuo
customThe crude product was purified by SiO2 chromatography
washeluting with a petroleum ether/EtOAc gradient (10 to 50% EtOAc)

Sources & evidence

ORD record: ord-2b30b26cddf745cbb7eb2fd4daa83cd9
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637537B2

Reaction notes

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