1,4-Dioxane → HCID 59371497, compound

Participants

Reaction Conditions

Reaction Steps

Palladium catalyst A (6.2 mg, 7.5 μmol, 83 mequiv.), 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (Xphos, 3.7 mg, 7.5 μmol, 83 mequiv.), tert-BuONa (206 mg, 2.1 mmol, 2.8 equiv.), 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]pyridine (268 mg, 0.75 mmol) and 3-azabicyclo[3.2.1]octane hydrochloride (Arkè Organics srl, Zona Industriale della Botte No. 4, 56012 Fornacette (PI), Italy; 133 mg, 0.90 mmol, 1.2 equiv.) were filled into a 25 mL round bottom-flask with a side neck. The flask was equipped with a stir bar, a condenser, and rubber septa. The atmosphere was exchanged with Ar (3 times), and anhydrous dioxane (3 mL) was added via syringe. The mixture was stirred at 100° C. for 5 h and cooled to room temperature. Water (10 mL) was added to quench the reaction. The product was extracted into EtOAc (40 mL). The organic phase was washed with brine (10 mL), dried over Na2SO4, and concentrated. The residue was purified by CC (SiO2, 25×2.5 cm, EtOAc) to give the crude product, which was further purified by preparative HPLC (Supelco Discovery C18, 250×21.2 mm, 5 μm particle size, UV detection at 270 nm, flow rate 12.5 mL/min, gradient from 20% to 100% CH3CN in water within 40 min, then 100% CH3CN for 20 min; tR 32.6-36.9 min) to give the title compound as a yellowish oil (198 mg, 65%). MS (EI) m/z 387 (M+, 16%).

Provenance & Evidence