Diethyl Malonate → HCID 118101242, compound

HRID 708832Notes

Reaction equation

HRID 708832 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].F[C:15]1[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[CH:30][C:16]=1[CH2:17][N:18]([CH3:29])[C:19](=[O:28])[O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CS(C)=O>[CH2:21]([O:20][C:19]([N:18]([CH2:17][C:16]1[CH:30]=[C:31]([N+:34]([O-:36])=[O:35])[CH:32]=[CH:33][C:15]=1[CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10])[CH3:29])=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 118092892HCID 118092892, compound

Product 1

HCID 118101242HCID 118101242, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To sodium hydride (60% dispersion) (1.885 g, 47.1 mmol), was added DMSO (20 mL). The mixture was stirred for 5 min, then diethyl malonate (7.15 mL, 47.1 mmol) was added. The reaction mixture was stirred at rt for 15 min to give a clear colorless solution. To this mixture was added a solution of benzyl 2-fluoro-5-nitrobenzyl(methyl)carbamate (3 g, 9.43 mmol) in DMSO (1 mL) dropwise. The orange reaction mixture was stirred at rt for 1 h, then at 65° C. for 3 h. The reaction mixture was cooled to rt, quenched with sat. NH4Cl. The mixture was diluted with EtOAc. The organic phase was washed with H2O (2×) and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (loaded in chloroform onto a 120 g column and eluted with a gradient from 0 to 30% ethyl acetate/hexanes) to give 10A (3.88 g, 8.46 mmol, 90% yield). MS (ESI) m/z: 458.9 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred at rt for 15 min
  2. customto give a clear colorless solution
  3. stirringThe orange reaction mixture was stirred at rt for 1 h
  4. waitat 65° C. for 3 h
  5. customquenched with sat. NH4Cl
  6. additionThe mixture was diluted with EtOAc
  7. washThe organic phase was washed with H2O (2×) and brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customThe crude product was purified by flash chromatography (
  11. washeluted with a gradient from 0 to 30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-fae2d5dc895941e8b2bccc8401ea6c22
Source dataset
uspto-grants-2015_11
Patent number
US09174974B2

Reaction notes

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