3,4-dihydro-2H-pyran → 5-bromo-7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole

HRID 475282Notes

Reaction equation

[Br:1][C:2]1[CH:10]=[C:9]([F:11])[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.CC1C=CC(S(O)(=O)=O)=CC=1.O>C1COCC1>[Br:1][C:2]1[CH:10]=[C:9]([F:11])[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

Conditions

Temperature: 80 °C

Procedure

To a solution of 5-bromo-7-fluoro-1H-benzo[d]imidazole (650 mg, 3.02 mmol, CASRN 1197944-33-2) and 3,4-dihydro-2H-pyran (1.27 g, 15.12 mmol) in THF (10 mL) was added p-TsOH.H2O (58 mg, 0.30 mmol). The reaction was stirred at 80° C. overnight, cooled and the solvent 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 in vacuo. The crude product was purified by SiO2 chromatography eluting with a petroleum ether/EtOAc gradient (10 to 50% EtOAc)) to afford 580 mg (64%) of 5-bromo-7-fluoro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole (266) as yellow solid: MS (ESI) m/z=299.1 [M+1]+.

Workup

temperaturecooled
customthe solvent 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 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-61af5ef545f14cfe9ff43a5a18a9dd47
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637537B2

Reaction notes

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