Ethyl Acetate → Diethyl 2-[2-(3-methyl-4'-nitro-1,1'-biphenyl-4-yl)-2-oxoethyl]-2-(2-phenylethyl)malonate

HRID 9560

Reaction equation

HRID 9560 reaction equation
[H-].[Na+].[C:3]1([CH2:9][CH2:10][CH:11]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br[CH2:23][C:24]([C:26]1[CH:31]=[CH:30][C:29]([C:32]2[CH:37]=[CH:36][C:35]([N+:38]([O-:40])=[O:39])=[CH:34][CH:33]=2)=[CH:28][C:27]=1[CH3:41])=[O:25].C(OCC)(=O)C>O1CCCC1.O>[CH3:41][C:27]1[CH:28]=[C:29]([C:32]2[CH:37]=[CH:36][C:35]([N+:38]([O-:40])=[O:39])=[CH:34][CH:33]=2)[CH:30]=[CH:31][C:26]=1[C:24](=[O:25])[CH2:23][C:11]([CH2:10][CH2:9][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1)([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 811191,3-Diethyl 2-(2-phenylethyl)propanedioateHCID 219856882-Bromo-1-(3-methyl-4'-nitro-1,1'-biphenyl-4-yl)ethanone

Product 1

HCID 21985780Diethyl 2-[2-(3-methyl-4'-nitro-1,1'-biphenyl-4-yl)-2-oxoethyl]-2-(2-phenylethyl)malonateYield 85.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a cold suspension (0–5° C.) of 95% sodium hydride (3.53 g, 13.0 mmol) in dry tetrahydrofuran (30 mL) was slowly added diethyl 2-phenylethylmalonate (3.53 g, 13 mmol). The ice bath was removed and the reaction mixture was stirred at rt for 45 minutes. A solution of 2-bromo-1-(3-methyl-4′-nitro-1,1′-biphenyl-4-yl)ethanone (4.06 g, 12.0 mmol) in dry tetrahydrofuran (50 mL) was slowly added, and the resulting mixture was stirred at rt for about 70 h. Ethyl acetate (80 mL) and water (20 mL) were added, and the layers were separated. The organic layer was washed with water (2×30 mL), dried over magnesium sulfate, and concentrated under reduced pressure to give a dark, brown oil. This material was purified by flash chromatography (10:90 ethyl acetate/hexane) to give diethyl 2-[2-(3-methyl-4′-nitro-1,1′-biphenyl-4-yl)-2-oxoethyl]-2-(2-phenylethyl)malonate as a light yellow oil (5.30 g, 82% yield). LC-MS ret. time 4.01 min, m/z 517.9 (MH+); 1H NMR (CDCl3) δ 1.23–1.35 (m, 6H), 2.41–2.50 (m, 2H), 2.56 (s, 3H), 2.59–2.66 (m, 3.71 (s, 2H), 4.21–4.32 (m, 4H), 7.13–7.19 (m, 3H), 7.22–7.30 (m, 2H), 7.49–7.55 (m, 2H), 7.73–7.82 (m, 3H), 8.31 (d, 2H).

Workup

  1. customThe ice bath was removed
  2. stirringthe resulting mixture was stirred at rt for about 70 h
  3. customthe layers were separated
  4. washThe organic layer was washed with water (2×30 mL)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give a dark, brown oil
  8. customThis material was purified by flash chromatography (10:90 ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a7e1c1360b964ec8b788fbdb3219f1f6
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Linked notes

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