Phosphorus oxychloride → 3-Bromo-2-chloro-4-(4-chlorophenyl)-6-methylpyridine

Temperature

100 °C

To a suspension of 3-bromo-4-(4-chlorophenyl)-6-methylpyridin-2(1H)-one (280 mg, 0.94 mmol) in phosphorus oxychloride (5 mL) was added anhydrous DMF (a few drops). The mixture was stirred at 100° C. for 7 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure to remove most of the phosphorus oxychloride. The remaining liquid was cooled at 0° C. and carefully quenched by addition of water. The resulting mixture was then adjusted to pH 7-8 by addition of saturated aqueous NaHCO3. The mixture was then extracted with EtOAc (30 mL×3). The combined EtOAc extracts were washed with saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified using a silica gel cartridge (12 g) eluted with a gradient of EtOAc (0-70%) in hexanes to obtain 180 mg (60%) of the title compound as a white solid. HPLC/MS: retention time=3.95 min, [M+H]+=316.0.

1. temperatureAfter cooling to room temperature
2. concentrationthe reaction mixture was concentrated under reduced pressure
3. customto remove most of the phosphorus oxychloride
4. temperatureThe remaining liquid was cooled at 0° C.
5. customcarefully quenched by addition of water
6. additionThe resulting mixture was then adjusted to pH 7-8 by addition of saturated aqueous NaHCO3
7. extractionThe mixture was then extracted with EtOAc (30 mL×3)
8. washThe combined EtOAc extracts were washed with saturated aqueous NaCl
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified
13. washeluted with a gradient of EtOAc (0-70%) in hexanes

ORD record

ord-d41f9769312f40278ff8d8bd952d5a76

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07572808B2