Diisopropylamine → (2R)-1-[2-(5-bromo-1-benzofuran-2-yl)ethyl]-2-methylpyrrolidine

Participants

Reaction Conditions

Reaction Steps

(2R)-2-Methylpyrrolidine tartrate (1.17 g, 5.0 mmol), and potassium carbonate (1.38 g, 10.0 mmol) were combined in acetonitrile (20 mL) and heated at 60° C. for 1 hour. The mixture was treated with 3-butynyl 4-methylbenzenesulfonate (673 mg, 3.0 mmol) and heated at about 60° C. overnight. The mixture was cooled to about 5° C. and filtered. The mixture was treated with the product from Example 3A (300 mg, 1.0 mmol), diisopropylamine (1.20 g, 11.8 mmol), dichlorobis(triphenylphosphine)palladium (II) (35.1 mg, 0.05 mmol), and copper iodide (38.0 mg, 0.20 mmol). After stirring overnight at about 30° C., the mixture was concentrated to dryness. The residue in ethyl acetate (20 mL) was washed with 5% NaHCO3 (20 mL×2) and 25% brine (25 mL). The organic phase was separated, dried over anhydrous Na2SO4, filtered, and the filtrate concentrated to dryness to provide the title compound. MS (esi): 308, 310 (M+H)+; 1H-NMR (CDCl3) δ 7.58 (1H, d, J=1.7 Hz), 7.27 (2H, m), 6.38 (1H, s), 3.20 (2H, m), 2.95 (2H, m), 2.43 (1H, m), 2.28 (1H, m), 2.19 (1H, q, J=8.8 Hz), 1.95 (1H, m), 1.75 (2H, m), 1.42 (1H, m), 1.13 (3H, d, J=6.2 Hz); 13C-NMR (CDCl3) δ 158.8, 152.9,130.6, 125.7, 122.6, 115.2,111.9, 101.8, 60.0, 53.9, 51.9, 32.9, 28.4, 22.0, 19.3.

Provenance & Evidence