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

Temperature

100 °C

To a suspension of 5-bromo-4-(4-chlorophenyl)-6-methylpyridin-2(1H)-one (300 mg, 1.0 mmol) in phosphorus oxychloride (5 mL) was added anhydrous DMF (0.015 mL). The mixture was stirred at 100° C. for 20 h. Analysis by HPLC/MS indicated about 27% of the starting 5-bromo-4-(4-chlorophenyl)-6-methylpyridin-2(1H)-one remained. Additional phosphorus oxychloride (1 mL) was added, followed by anhydrous DMF (0.1 mL). The reaction mixture was stirred at 100° C. for 24 h more. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure to remove most of the phosphorus oxychloride. The residue was dissolved in EtOAc, washed with saturated aqueous NaHCO3, then saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (12 g) eluted with a gradient of EtOAc (20-40%) in hexanes to obtain 220 mg (70%) of the title compound as a white solid. HPLC/MS: retention time=4.07 min, [M+H]+=316.2.

1. stirringThe reaction mixture was stirred at 100° C. for 24 h more
2. temperatureAfter cooling to room temperature
3. concentrationthe reaction mixture was concentrated under reduced pressure
4. customto remove most of the phosphorus oxychloride
5. dissolutionThe residue was dissolved in EtOAc
6. washwashed with saturated aqueous NaHCO3
7. dry with materialsaturated aqueous NaCl, dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe crude product was purified
11. washeluted with a gradient of EtOAc (20-40%) in hexanes

ORD record

ord-aa07b7da3a644c89b17c7749f0bc4d71

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07572808B2