Reaction #9632

Reaction equation

Methyl 4-[2-(4-bromophenyl)-2-oxoethyl]tetrahydro-2H-pyran-4-carboxylate

4-nitrophenyl boronic acid

sodium carbonate

dichloromethane

→

methyl 4-[2-(4′-nitro-1,1′-biphenyl-4-yl)-2-oxoethyl]tetrahydro-2H-pyran-4-carboxylate

Yield 79.3%

Solvents

Water

dioxane

Toluene

Conditions

Workup

1. 1
   Otherthe resulting solution was degassed for 30 minutes by a flow of argon
2. 2
   Temperaturewas cooled to rt
3. 3
   Extractionthe aqueous layer was extracted twice with ethyl acetate
4. 4
   DryingThe combined organic phases were then dried over anhydrous sodium sulfate
5. 5
   Concentrationconcentrated under reduced pressure
6. 6
   OtherThe resulting residue was purified by flash chromatography (Biotage Flash 40)

Procedure

Methyl 4-[2-(4-bromophenyl)-2-oxoethyl]tetrahydro-2H-pyran-4-carboxylate (820 mg, 2.40 mmol) and 4-nitrophenyl boronic acid (481 mg, 2.88 mmol) were combined in a dry flask under argon. Toluene (20 mL) and dioxane (5 mL) were added, and the resulting solution was degassed for 30 minutes by a flow of argon. The degassing was continued during the addition of saturated aqueous sodium carbonate (6 mL) and [1,1′-bis(diphenylphosphino)-ferrocene]dichloro palladium(II), 1:1 complex with dichloromethane (98 mg, 0.12 mmol). The resulting mixture was then heated at 85° C. for 16 h before it was cooled to rt. Water was added, and the aqueous layer was extracted twice with ethyl acetate. The combined organic phases were then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (Biotage Flash 40) using 1:1 ethyl acetate/hexane to afford methyl 4-[2-(4′-nitro-1,1′-biphenyl-4-yl)-2-oxoethyl]tetrahydro-2H-pyran-4-carboxylate (730 mg, 79%). LC-MS ret. time 3.03; m/z 383.9 (MH+); 1H NMR (300 MHz, CDCl3) δ 1.65–1.73 (m, 2H), 2.17–2.21 (m, 2H), 3.37 (s, 2H), 3.68 (s, 3H), 3.71–3.78 (m, 4H), 7.70 (d, 2H), 7.77 (d, 2H), 8.02 (d, 2H), 8.31 (d, 2H).

Source