3-Methylisoquinoline → Tert-butyl 3-(3-methylisoquinolin-1-yl)azetidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

H2O2 (30% in H2O; 0.31 mL, 3.0 mmol) was added over 1 min to a stirred solution of 3-methylisoquinoline 1c (143 mg, 1.0 mmol), concentrated H2SO4 (107 μL, 2.0 mmol), 1-Boc-3-(iodo)azetidine (566 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, 0.3 mmol) was added and the mixture was stirred at 40 °C for 25 min. Further H2O2 (0.31 mL, 3.0 mmol) and iron(II) sulfate heptahydrate (80 mg, 0.3 mmol) was added, and the mixture was stirred at 40 °C for another 25 min, then poured into a 0.2 M solution of NaOH (30 mL) and Et2O (50 mL). The aqueous and organic layers were partitioned and the aqueous was extracted with Et2O (2 x 25 mL) and EtOAc (1 x 25 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 (617 mg). The oil was purified by column chromatography on silica gel using EtOAc / hexanes (0:1 to 1:4) as eluent to give the product contaminated with DMSO. The product was dissolved in Et2O (10 mL) and washed with brine (3 x 8 mL), dried (Na2SO4), filtered and the solvent removed under vacuum to leave a crude oil (165 mg). The oil was purified further using column chromatography on silica gel using EtOAc / hexanes (0:1 to 1:4) as eluent to give the desired product 3c (61 mg, 20%) as an oil

Provenance & Evidence