1H-Benzimidazole, 1-methyl- → HCID 44239812, compound

Temperature

60 °C

H2O2 (30% in H2O; 0.31 mL, 3.0 mmol) was added dropwise over 1-2 min to a stirred solution of 1-methylbenzimidazole 1g (100 mg, 1.0 mmol), concentrated H2SO4 (107 μL, 2.0 mmol), 3-iodooxetane (368 mg, 2.0 mmol) and iron(II) sulfate heptahydrate (80 mg, 0.3 mmol) in DMSO (10 mL) at room temperature. After 30 min a further portion of iron(II) sulfate heptahydrate (200 mg, 0.75 mmol) and H2O2 (0.31 mL, 3.0 mmol) was added, and the mixture was stirred at room temperature for 30 min. Further iron(II) sulfate heptahydrate (200 mg, 0.75 mmol) and H2O2 (0.31 mL, 3.0 mmol) was added and the mixture stirred at room temperature for 120 min, then heated to 60 °C and stirred for 60 min. After allowing to cool, the mixture was poured into a solution of NaOH and ice (to pH > 10) and it was then extracted with Et2O. The aqueous layer was saturated with solid NaCl and extracted with CHCl3. The combined organic extracts were dried (MgSO4), filtered and the solvent removed under vacuum to leave a crude residue. The residue was purified by column chromatography on silica gel using EtOAc / MeOH (1:0 to 4:1) to give impure product (40 mg). The impure product was purified further by preparative thin-layer chromatography using EtOAc / MeOH (19:1) as eluent to give product (25 mg). The product was purified further using preparative high-performance liquid chromatography using 0.1% aqueous formic acid / MeCN (19:1 to 9:1) as eluent to give the desired product 2g (12 mg, 6%) as a solid.

ORD record

ord-98133d0b8a69408ba939cadb7f0b7452

Source dataset

Minisci dataset from Roche

DOI

10.1021/jo9010624