Water → N-(5-Bromo-2-methoxypyridin-3-yl)methanesulfonamide

Temperatur

105 °C

To a 20 mL scintillation vial, 5-bromo-3-iodo-2-methoxypyridine (Alfa Aesar, 2.02 g, 6.43 mmol), methanesulfonamide (Fluka, 0.645 g, 6.78 mmol), copper (I) iodide (Strem, 0.122 g, 0.643 mmol), cesium carbonate (Aldrich, 5.27 g, 16.1 mmol) and water (0.60 ml, 33.3 mmol) were mixed into DMF (6 mL). The reaction mixture was stirred at 105° C. for overnight. Then the mixture was heated in a microwave reactor (Biotage) at 120° C. for 30 min. The reaction mixture was partitioned between Tris-HCl buffer (1 M, pH 7.0) (20 mL) and EtOAc (20 mL). The aq phase was extracted with EtOAc (2×20 mL). The combined organic phases were washed with saturated aq NaCl (40 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford the crude product, which was purified by silica gel column chromatography (100 g, eluent: EtOAc in hexanes 0% to 50%) to afford N-(5-bromo-2-methoxypyridin-3-yl)methanesulfonamide (1.06 g, 59% yield) as a white solid. 1H NMR (300 MHz, CDCl3) δ ppm 7.97 (d, J=2.19 Hz, 1H) 7.90 (d, J=2.19 Hz, 1H) 6.72 (br. s., 1H) 4.00 (s, 3H) 3.04 (s, 3H). m/z (ESI, positive ion): 280.8, 282.8 [M+1, M+3].

1. temperatureThen the mixture was heated in a microwave reactor (Biotage) at 120° C. for 30 min
2. customThe reaction mixture was partitioned between Tris-HCl buffer (1 M, pH 7.0) (20 mL) and EtOAc (20 mL)
3. extractionThe aq phase was extracted with EtOAc (2×20 mL)
4. washThe combined organic phases were washed with saturated aq NaCl (40 mL)
5. dry with materialThe organic phase was dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto afford the crude product, which
9. customwas purified by silica gel column chromatography (100 g, eluent: EtOAc in hexanes 0% to 50%)

ORD-Eintrag

ord-ae03be40603346f0b03f9df56b29e404

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08772480B2