Reaktion #9648

Reaktionsgleichung

2-fluoro-4-iodophenylformamide

potassium acetate

methyl (R,R)-2-(4-bromobenzoyl)cyclopentanecarboxylate

cesium carbonate

→

methyl 2-{[3′-fluoro-4′-(formylamino)-1,1′-biphenyl-4-yl]carbonyl}cyclopentanecarboxylate

Ausbeute 169.4%

Lösungsmittel

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigewas bubbled through argon for 30 minutes
2. 2
   TemperaturAfter the mixture was cooled to rt
3. 3
   Temperaturthe reaction mixture was then heated at 80° C. for 16 h
4. 4
   TemperaturThe mixture was then cooled to rt
5. 5
   Sonstigequenched with water
6. 6
   Extraktionextracted with ethyl acetate
7. 7
   Trocknendried over anhydrous sodium sulfate
8. 8
   SonstigeSolvent was then removed under reduced pressure
9. 9
   Sonstigethe crude product was purified by flash chromatography (Biotage 75)

Vorschrift

To a suspension of 2-fluoro-4-iodophenylformamide (5.11 g, 19.28 mmol) bis(pinacolato)diboron (4.89 g, 19.28 mmol), potassium acetate (5.67 g, 57.84 mmol), and palladium acetate (129 mg, 0.58 mmol) in N,N-dimethylformamide (125 mL) was bubbled through argon for 30 minutes. The reaction mixture was then heated at 80° C. for 3 h. After the mixture was cooled to rt, methyl (R,R)-2-(4-bromobenzoyl)cyclopentanecarboxylate (2.2 g, 7.35 mmol, 97% ee), tetrakis(triphenylphosphine)palladium(0) (668 mg, 0.58 mmol), and cesium carbonate (9.43 g, 28.92 mmol) were added, and the reaction mixture was then heated at 80° C. for 16 h. The mixture was then cooled to rt, quenched with water, extracted with ethyl acetate, and dried over anhydrous sodium sulfate. Solvent was then removed under reduced pressure and the crude product was purified by flash chromatography (Biotage 75) using 1:1 ethylacetate/hexane to afford methyl 2-{[3′-fluoro-4′-(formylamino)-1,1′-biphenyl-4-yl]carbonyl}cyclopentanecarboxylate (4.6 g, 65%). LC-MS ret. time 3.15 min, m/z 342.0 (MH+); 1H NMR (300 MHz, DMSO-d6) δ 1.52–1.94 (m, 1H), 1.92–2.07 (m, 1H), 2.10–2.21 (m, 1H), 3.48 (m, 1H), 3.55 (s, 3H), 4.12 (q, 1H), 7.59 (dd, 1H), 7.62 (dd, 1H), 7.87 (d, 2H), 8.09 (d, 2H), 8.25 (t, 1H), 8.34 (s, 1H), 10.62 (s, 1H).

Quelle