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

Temperature

60 °C

(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.

1. temperatureheated at about 60° C. overnight
2. temperatureThe mixture was cooled to about 5° C.
3. filtrationfiltered
4. concentrationthe mixture was concentrated to dryness
5. washThe residue in ethyl acetate (20 mL) was washed with 5% NaHCO3 (20 mL×2) and 25% brine (25 mL)
6. customThe organic phase was separated
7. dry with materialdried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationthe filtrate concentrated to dryness

ORD record

ord-4719ed18c1af4091abfc23a7f991e5a7

Source dataset

uspto-grants-2004_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06822101B2