Reacción #9650

Ecuación de reacción

2-fluoro-4-iodophenylformamide

bis(pinacolato)diboron

potassium acetate

methyl 4-(4-bromophenyl)-2,2-dimethyl-4-oxobutanoate

cesium carbonate

→

methyl 4-[3′-fluoro-4′-(formylamino)-1,1′-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate

Rendimiento 46.0%

Disolventes

N,N-dimethylformamide

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas degassed
2. 2
   Otroby bubbling a flow of argon through the mixture for 30 minutes
3. 3
   TemperaturaAfter the mixture was cooled to rt
4. 4
   Temperaturathe reaction mixture was heated at 80° C. for 16 h
5. 5
   TemperaturaThe mixture was then cooled to rt
6. 6
   ExtracciónThe mixture was extracted with ethyl acetate
7. 7
   Secadothe combined extracts were dried over sodium sulfate
8. 8
   ConcentraciónThe mixture was concentrated under reduced pressure
9. 9
   Otrothe crude was purified by flash chromatography (Biotage Flash 40M, 1:1 ethyl acetate/hexane)

Procedimiento

A suspension of 2-fluoro-4-iodophenylformamide (1.94 g, 7.35 mmol, prepared as described above), bis(pinacolato)diboron (1.86 g, 7.35 mmol), potassium acetate (2.16 g, 22.1 mmol), and palladium acetate (49.4 mg, 0.22 mmol) in N,N-dimethylformamide (50 mL) was degassed by bubbling a flow of argon through the mixture for 30 minutes. The mixture was then heated at 80° C. for 3 h. After the mixture was cooled to rt, methyl 4-(4-bromophenyl)-2,2-dimethyl-4-oxobutanoate (2.2 g, 7.4 mmol), tetrakis(triphenylphosphine)palladium(0) (254.8 mg, 0.22 mmol), and cesium carbonate (3.59 g, 11.0 mmol) were added, and the reaction mixture was heated at 80° C. for 16 h. The mixture was then cooled to rt and water was added. The mixture was extracted with ethyl acetate and the combined extracts were dried over sodium sulfate. The mixture was concentrated under reduced pressure and the crude was purified by flash chromatography (Biotage Flash 40M, 1:1 ethyl acetate/hexane) to afford methyl 4-[3′-fluoro-4′-(formylamino)-1,1′-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate (1.2 g, 46%). LC-MS ret. time 2.80 min, m/z 358.1 (MH+); 1H NMR (300 MHz, DMSO-d6) δ 1.19 (s, 6H), 3.36 (s, 2H), 3.51 (s, 3H), 7.56 (d, 1H), 7.69 (dd, 1H), 7.82 (d, 2H), 7.99 (d, 3H), 8.21 (t), 10.25 (s, 1H).

Fuente