Toluene → Ethyl 4-(4'-nitro-1,1'-biphenyl-4-yl)-4-oxo-2-(2-phenylethyl)butanoate

HRID 9525

Reaction equation

HRID 9525 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:24])[CH2:9][CH:10]([CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:4][CH:3]=1.[N+:25]([C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1)([O-:27])=[O:26].C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[N+:25]([C:28]1[CH:33]=[CH:32][C:31]([C:2]2[CH:7]=[CH:6][C:5]([C:8](=[O:24])[CH2:9][CH:10]([CH2:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:4][CH:3]=2)=[CH:30][CH:29]=1)([O-:27])=[O:26]

Participants

6

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27735524-Nitrophenylboronic acidHCID 21985805Ethyl 4-(4-bromophenyl)-4-oxo-2-(2-phenylethyl)butanoate

Product 1

HCID 21985737Ethyl 4-(4'-nitro-1,1'-biphenyl-4-yl)-4-oxo-2-(2-phenylethyl)butanoateYield 75.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

Ethyl 4-(4-bromophenyl)-4-oxo-2-(2-phenylethyl)butanoate (4.32 g, 11.1 mmol) and 4-nitrophenylboronic acid (2.22, 13.3 mmol) was added to a dry flask under argon. Toluene (100 mL), dioxane (25 mL), saturated aqueous sodium carbonate (30 mL), and [1,1′-bis(diphenyl-phosphino)-ferrocene]dichloro palladium(II) (1:1 complex with dichloromethane, 453 mg, 0.55 mmol) were added and the mixture was thoroughly degassed. The resulting mixture was then heated at 85° C. for 16 h before it was cooled to rt. Water was added and the mixture was extracted twice with ethyl acetate. The combined extracts were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography (Biotage flash 75, 5:1 ethyl acetate/hexane) to afford ethyl 4-(4′-nitro-1,1′-biphenyl-4-yl)-4-oxo-2-(2-phenylethyl)butanoate (3.6 g, 75%). HPLC ret. time 3.99 min, 1H NMR (300 MHz, CDCl3) δ 1.29 (t, 3H), 1.85–2.08 (m, 2H), 2.71 (t, 2H), 3.05–3.20 (m, 2H), 3.45–3.52 (m, 1H), 4.20 (q, 2H), 7.18–7.31 (m, 5H), 7.72 (d, 2H), 7.78 (d, 2H), 8.05 (d, 2H), 8.33 (d, 2H).

Workup

  1. customthe mixture was thoroughly degassed
  2. temperaturewas cooled to rt
  3. additionWater was added
  4. extractionthe mixture was extracted twice with ethyl acetate
  5. dry with materialThe combined extracts were dried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography (Biotage flash 75, 5:1 ethyl acetate/hexane)

Sources & evidence

ORD record
ord-401204b21f9244dfb803dad51a9352ec
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Linked notes

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