Reacción #9652

Ecuación de reacción

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

bis(pinacolato)diboron

potassium acetate

5-chloro-2-nitroanisole

cesium carbonate

→

methyl 4-(3′-methoxy4′-nitro-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoate

Rendimiento 48.2%

Disolventes

N,N-dimethylformamide

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas degassed
2. 2
   Otroby bubbling a flow of argon 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 aqueous layer was extracted with ethyl acetate
7. 7
   Secadothe combined organic phases were dried over anhydrous sodium sulfate
8. 8
   OtroSolvent was removed under reduced pressure
9. 9
   Otrothe residue was purified by flash chromatography (Biotage Flash 40M, 1:3 ethyl acetate/hexane)

Procedimiento

A suspension of methyl 4-(4-bromophenyl)-2,2-dimethyl-4-oxobutanoate (200 mg, 0.67 mmol), bis(pinacolato)diboron (170 mg, 0.67 mmol), potassium acetate (197 mg, 2.01 mmol), and palladium acetate (5 mg, 0.02 mmol) in N,N-dimethylformamide (4.0 mL) was degassed by bubbling a flow of argon for 30 minutes. The reaction mixture was then heated at 80° C. for 3 h. After the mixture was cooled to rt, 5-chloro-2-nitroanisole (125 mg, 0.67 mmol), tetrakis(triphenyl-phosphine)palladium(0) (23 mg, 0.02 mmol), and cesium carbonate (327 mg, 1.0 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 aqueous layer was extracted with ethyl acetate and the combined organic phases were dried over anhydrous sodium sulfate. Solvent was removed under reduced pressure and the residue was purified by flash chromatography (Biotage Flash 40M, 1:3 ethyl acetate/hexane) to afford methyl 4-(3′-methoxy4′-nitro-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoate (120 mg, 48%). LC-MS ret. time 3.38 min, m/z 371.8 (MH+); 1H NMR (300 MHz, CDCl3) δ 1.19 (s, 6H), 3.36 (s, 2H), 3.51 (s, 3H), 4.02 (s, 3H), 7.21–7.24 (m, 2H), 7.64–7.69 (m, 2H), 7.93 (d, 1H), 8.00–8.04 (m, 2H).

Fuente