3,6-Dimethoxypyridazine → Tert-butyl 3-(3,6-dimethoxypyridazin-4-yl)azetidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

H2O2 (30% in H2O; 0.15 mL, 1.5 mmol) was added over 1 min to a stirred solution of 3,6-dimethoxypyridazine 1e (67 mg, 0.5 mmol), concentrated H2SO4 (51 μL, 1.0 mmol), 1-Boc-3-(iodo)azetidine (271 mg, 1.0 mmol) and iron(II) - 14 -sulfate heptahydrate (40 mg, 0.15 mmol) in DMSO (5 mL) at room temperature. The mixture was then placed in an oil bath at 60 °C. After 2 min a further portion of iron(II) sulfate heptahydrate (40 mg, 0.15 mmol) was added and the mixture was stirred at 60 °C for 30 min. Further H2O2 (0.15 mL, 1.5 mmol) and iron(II) sulfate heptahydrate (40 mg, 0.15 mmol) was added, and the mixture was stirred at 60 °C for another 30 min. A final aliquot of H2O2 (0.15 mL, 1.5 mmol) and iron(II) sulfate heptahydrate (40 mg, 0.15 mmol) was added and the mixture was stirred at 60 °C for another 30 min. After allowing to cool, the mixture was poured into a 0.2 M solution of NaOH (15 mL) and Et2O (25 mL). The aqueous and organic layers were partitioned and the aqueous was extracted with Et2O (2 x 15 mL). The combined organic layers were washed with brine (25 mL), dried (MgSO4), filtered and the solvent removed under vacuum to leave a crude oil (408 mg). The oil was purified by column chromatography on silica gel using EtOAc / hexanes (0:1 to 1:1) as eluent to give the desired product 3d (57 mg, 41%) as an oil

Provenance & Evidence