Dimethylformamide → Dimethyl [2-(4-fluoro-2-nitrophenyl)-1-phenylethyl]malonate

HRID 2267607Notes

Reaction equation

HRID 2267607 reaction equation
C1(=O)O[CH:6](C2C=CC=CC=2)[O:5][C:3](=[O:4])C1.[H-].[Na+].[F:17][C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[C:20]([N+:25]([O-:27])=[O:26])[CH:19]=1.[CH3:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33].[C:34]([O:37][CH2:38]C)(=[O:36])[CH3:35].[CH3:40]N(C=O)C>>[CH3:6][O:5][C:3](=[O:4])[CH:35]([CH:40]([C:30]1[CH:29]=[CH:28][CH:33]=[CH:32][CH:31]=1)[CH2:24][C:21]1[CH:22]=[CH:23][C:18]([F:17])=[CH:19][C:20]=1[N+:25]([O-:27])=[O:26])[C:34]([O:37][CH3:38])=[O:36]

Participants

6

Reactant 5

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 679654-Fluoro-2-nitrotolueneHCID 9338292-Phenyl-1,3-dioxane-4,6-dioneHCID 21226206Ethyl acetate hexane2×

Product 1

HCID 59688514Dimethyl [2-(4-fluoro-2-nitrophenyl)-1-phenylethyl]malonateYield 30%

Procedure

A solution of benzylidene malonate (14.2 g) in DMF (280 mL) was treated with sodium hydride (2.57 g, 95%). A solution of 4-fluoro-2-nitrotoluene in DMF (10 mL) was added over 1H, and the reaction mixture was stirred at RT overnight and then quenched by the addition of glacial acetic acid (175 mL) at 0° C. A total of 500 mL of 70:30 water-methanol was added with stirring, and the organics were extracted with ethyl acetate. The organic extracts were combined and washed with saturated aqueous potassium carbonate solution (2×) and brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give a dark brown oil. Flash chromatography on silica gel (75:25 hexane-ethyl acetate, then 50:50 hexane-ethyl acetate) provided 7.0 g (30%) of the title compound as a red-brown solid. 1H NMR (300 MHz, CDCl3) δ 3.72 (d, 2H), 3.73 (d, 1H), 4.32 (m, 1H), 7.09-7.29 (m, 7H), 7.71 (m, 1H). MS APCI, m/z=398 (M+Na). LC/MS: 2.66 min.

Workup

  1. customquenched by the addition of glacial acetic acid (175 mL) at 0° C
  2. additionA total of 500 mL of 70:30 water-methanol was added
  3. stirringwith stirring
  4. extractionthe organics were extracted with ethyl acetate
  5. washwashed with saturated aqueous potassium carbonate solution (2×) and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a dark brown oil

Sources & evidence

ORD record
ord-d1c05d2a8f4d47f5ba7021ba682c1f15
Source dataset
uspto-grants-2010_12
Patent number
US07858776B2

Reaction notes

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