Reaktion #59147

Reaktionsgleichung

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

Ausbeute 46.0%

Lösungsmittel

N,N-dimethylformamide

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas degassed
2. 2
   Sonstigeby bubbling a flow of argon through the mixture for 30 minutes
3. 3
   TemperaturAfter the mixture was cooled to rt
4. 4
   Temperaturthe reaction mixture was heated at 80° C. for 16 h
5. 5
   TemperaturThe mixture was then cooled to rt
6. 6
   ExtraktionThe mixture was extracted with ethyl acetate
7. 7
   Trocknenthe combined extracts were dried over sodium sulfate
8. 8
   EinengenThe mixture was concentrated under reduced pressure
9. 9
   Sonstigethe crude was purified by flash chromatography (Biotage Flash 40M, 1:1 ethyl acetate/hexane)

Vorschrift

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).

Quelle