(5-Ethyl-1-azabicyclo(2.2.2)octan-2-yl)(6-methoxyquinolin-4-yl)methanol → tert-butyl 3-[4-[(5-ethyl-1-azabicyclo[2.2.2]octan-2-yl)-hydroxymethyl]-6-methoxyquinolin-2-yl]azetidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

H2O2 (30% in H2O; 0.31 mL, 3.0 mmol) was added dropwise over 1-2 min to a stirred solution of 6-methoxy-4-methylquinoline 4a (173 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 1-2 min a further portion of iron(II) sulfate heptahydrate (80 mg, 0.3 mmol) was added and the mixture was stirred at room temperature for 30 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 for 15 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 layer was extracted with Et2O (2 x 25 mL). The combined organic extracts were dried (MgSO4), filtered and the - 16 -solvent removed under vacuum to leave a crude oil. The oil was purified by preparative thin-layer chromatography using 30% EtOAc / hexanes as eluent to give recovered 6-methoxy-4-methylquinoline 4a (32 mg, 19%), a mixture of 6-methoxy-4-methylquinoline 4a and the desired product 5a (15 mg) and the desired product 5a (72 mg, 31%) as a solid. An analytical portion of the product 5a was recrystallized from hexanes for data purposes

Provenance & Evidence