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

Temperature

60 °C

(2R)-2-Methylpyrrolidine tartrate (0.70 g, 3.0 mmol) and potassium carbonate (0.82 g, 6.0 mmol) were combined in acetonitrile (12 mL). The slurry was heated at 60° C. for 1 hour, treated with the product from Example 4B (790 mg, 2.0 mmol). The mixture was heated at about 60° C. for 6 hours, cooled to 25° C., and diluted with toluene (30 mL). The mixture was washed with 5% NaHCO3 (40 mL×2) and extracted with H2O: N-methylpyrrolidinone: MSA (methanesulfonic acid)=70:20:10 (30 mL). The aqueous solution was adjusted to pH about 12 with 50% NaOH and extracted with IPAC (45 mL). The organic phase was washed with 5% NaHCO3 (50 mL×3), water (50 mL, 2×), dried over MgSO4, filtered, and the filtrate was concentrated to dryness to provide 375 mg (60%) of 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 (2 H, m), 2.95 (2H, m), 2.43 (1H, m), 2.28 (1H, m), 2.19 (1H, q, J=8.8 Hz), 1.95 (1 H, 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. temperatureThe mixture was heated at about 60° C. for 6 hours
2. temperaturecooled to 25° C.
3. washThe mixture was washed with 5% NaHCO3 (40 mL×2)
4. extractionextracted with H2O
5. extractionextracted with IPAC (45 mL)
6. washThe organic phase was washed with 5% NaHCO3 (50 mL×3), water (50 mL, 2×)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationthe filtrate was concentrated to dryness

ORD record

ord-5994a6628c1849eba3dd453fd7d1c561

Source dataset

uspto-grants-2004_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06822101B2