Hydrochloric Acid → 2-Chloro-2'-fluoro-5-methoxy-[1,1'-biphenyl]-4-carboxylic acid

To a stirred solution of 4-iodo-5-chloro-2-methoxy benzoic acid of Example 15, Step A (3.72 g, 19.1 mmol) in N,N-dimethylformamide (20 mL) was added 2-fluorophenyl boronic acid (5.0 g, 35.7 mmol) and potassium carbonate (14.8 g, 107 mmol). This mixture was purged with nitrogen and then treated with a catalytic amount of tetrakis(triphenylphosphine) palladium(0) (0.688 g, 0.59 mmol). The reaction was heated to reflux overnight, cooled, acidified with 2 N hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. The residue was flash chromatographed on acid washed silica using a 10 to 50% gradient of diethyl ether in hexane to provide the desired title compound (3.8 g) as a white solid.

1. customThis mixture was purged with nitrogen
2. temperatureThe reaction was heated
3. temperatureto reflux overnight
4. temperaturecooled
5. extractionextracted with ethyl acetate
6. washThe organic layer was washed with brine
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. customevaporated to dryness
10. customchromatographed on acid
11. washwashed silica using a 10 to 50% gradient of diethyl ether in hexane

ORD record

ord-a0211ca356d64a1d8220cc46da74f83c

Source dataset

uspto-grants-2006_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07064120B2