Reaktion #1917270

Reaktionsgleichung

hydrochloric acid

4-iodo-5-chloro-2-methoxy benzoic acid

2-Chloro-2′-ethoxy-5-methoxy-[1,1′-biphenyl]-4-carboxylic acid

2-fluorophenyl boronic acid

potassium carbonate

→

desired title compound

Ausbeute 70.9%

2-Chloro-2′-fluoro-5-methoxy-[1,1′-biphenyl]-4-carboxylic acid

Ausbeute 70.9%

Lösungsmittel

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThis mixture was purged with nitrogen
2. 2
   TemperaturThe reaction was heated
3. 3
   Temperaturto reflux overnight
4. 4
   Temperaturcooled
5. 5
   Extraktionextracted with ethyl acetate
6. 6
   WaschenThe organic layer was washed with brine
7. 7
   Trocknendried over anhydrous magnesium sulfate
8. 8
   Filtrationfiltered
9. 9
   Sonstigeevaporated to dryness
10. 10
    Sonstigechromatographed on acid
11. 11
    Waschenwashed silica using a 10 to 50% gradient of diethyl ether in hexane

Vorschrift

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.

Quelle