Potassium Carbonate → 3-(3-Bromo-5-chlorophenoxy)-2-chloro-4-(trifluoromethyl)pyridine

To a round bottom flask charged with 3-bromo-5-chlorophenol (5.20 g, 25.1 mmol) and potassium carbonate (3.46 g, 25.1 mmol) was added N-methylpyrrolidinone (25 mL). To this suspension under N2 was added 2-chloro-3-fluoro-4-(trifluoromethyl)pyridine (5.00 g, 25.1 mmol) and the reaction mixture was placed in an oil bath at 120° C. After 60 minutes, the reaction mixture was allowed to cool to room temperature at which point, water (100 mL) was added. The mixture was extracted with ethyl acetate (2×100 mL) and the combined organic fractions were washed with brine (3×100 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The resulting residue was adsorbed onto silica gel and purified by column chromatography on a pre-packed silica gel Redi Sep 330 gram column, eluting with 0-75% CH2Cl2 in hexanes to yield the title compound. 1H NMR (CDCl3) δ 8.53 (d, J=5.0 Hz, 1H), 7.62 (d, J=5.0 Hz, 1H), 7.29-7.27 (m, 1H), 6.87-6.84 (m, 1H), 6.76-6.73 (m, 1H). FIRMS (M+1)=385.8957.

1. customthe reaction mixture was placed in an oil bath at 120° C
2. additionwas added
3. extractionThe mixture was extracted with ethyl acetate (2×100 mL)
4. washthe combined organic fractions were washed with brine (3×100 mL)
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. customthe solvent was evaporated under reduced pressure
8. custompurified by column chromatography on a pre-packed silica gel Redi Sep 330 gram column
9. washeluting with 0-75% CH2Cl2 in hexanes

ORD record

ord-2d65a81e15f24be5b9a3ae4ea955205b

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08404856B2