3-Methylisoquinoline → HCID 44239662, compound

Participants

Reaction Conditions

Reaction Steps

H2O2 (30% in H2O; 0.31 mL, 3.0 mmol) was added dropwise over 3 min to a stirred solution of 3-methylisoquinoline 1c (143 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 40 °C. After 3 min a further portion of iron(II) sulfate heptahydrate (80 mg, - 5 -(80 mg, 0.3 mmol) was added and the mixture was stirred at 40 °C for 30 min. Further H2O2 (0.31 mL, 3.0 mmol) and iron(II) sulfate heptahydrate (80 mg, 0.3 mmol) was added over 2 min, and the mixture was stirred at 40 °C for 20 min, then poured into 0.2 M solution of NaOH (20 mL) and Et2O (50 mL). The aqueous and organic layers were partitioned and the aqueous layer was extracted with Et2O (2 x 25 mL). The combined organic extracts were washed with brine (25 mL), dried (MgSO4), filtered and the solvent removed under vacuum to leave a crude oil (364 mg). The oil was dry-loaded on to silica (750 mg) and purified by column chromatography on silica gel using EtOAc / hexanes (0:1 to 3:7) to give the desired product 2c (99 mg, ca. 93% purity, 46% yield adjusted for purity) as a solid. The solid was purified further by column chromatography on silica gel using EtOAc / hexanes (0:1 to 1:4 slow gradient then to 3:7) as eluent (to give 67 mg, 96% purity), then by recrystallization from methylcyclohexane to give material for data purposes.

Provenance & Evidence