Réaction #9652

Équation de réaction

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

Rendement 48.2%

Solvants

N,N-dimethylformamide

water

Conditions de réaction

Traitement

1. 1
   Autrewas degassed
2. 2
   Autreby bubbling a flow of argon for 30 minutes
3. 3
   TempératureAfter the mixture was cooled to rt
4. 4
   Températurethe reaction mixture was heated at 80° C. for 16 h
5. 5
   TempératureThe mixture was then cooled to rt
6. 6
   ExtractionThe aqueous layer was extracted with ethyl acetate
7. 7
   Séchagethe combined organic phases were dried over anhydrous sodium sulfate
8. 8
   AutreSolvent was removed under reduced pressure
9. 9
   Autrethe residue was purified by flash chromatography (Biotage Flash 40M, 1:3 ethyl acetate/hexane)

Mode opératoire

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).

Source