Dimethyl malonate → HCID 59389403, compound

HRID 2357919Notes

Reaction equation

HRID 2357919 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[H-].[Na+].[CH2:12]([C:14]1[CH:28]=[C:17]2[C:18]([C:23](=[O:27])[CH:24](Br)[CH3:25])=[CH:19][C:20]([F:22])=[CH:21][N:16]2[N:15]=1)[CH3:13]>CN(C=O)C>[CH2:12]([C:14]1[CH:28]=[C:17]2[C:18]([C:23](=[O:27])[CH:24]([CH:2]([C:1]([O:8][CH3:9])=[O:7])[C:3]([O:5][CH3:6])=[O:4])[CH3:25])=[CH:19][C:20]([F:22])=[CH:21][N:16]2[N:15]=1)[CH3:13]

Participants

5

Reactant 3

HCID 7943Dimethyl malonateHCID 24758Sodium hydrideHCID 59389306HCID 59389306, compound

Product 1

HCID 59389403HCID 59389403, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Dimethyl malonate (327 μL) was added to DMF (4.6 mL) in an argon atmosphere. While the solution was kept at 0° C., 60% sodium hydride (105 mg) was added and the mixture was stirred at room temperature for 30 min. Subsequently, the compound of Example 188 (655 mg) in DMF (10 mL) was added at 0° C. and the mixture was stirred at room temperature for 4 hours. The reaction was terminated by adding a saturated aqueous solution of ammonium chloride and the mixture was extracted three times with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. Evaporation of the solvent under reduced pressure and purification by silica gel column chromatography (hexane:ethyl acetate=6:1) afforded the title compound as a yellow oil (680 mg).

Workup

  1. customwas kept at 0° C.
  2. stirringthe mixture was stirred at room temperature for 4 hours
  3. customThe reaction was terminated
  4. additionby adding a saturated aqueous solution of ammonium chloride
  5. extractionthe mixture was extracted three times with ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over sodium sulfate
  8. customEvaporation of the solvent
  9. customunder reduced pressure and purification by silica gel column chromatography (hexane:ethyl acetate=6:1)

Sources & evidence

ORD record
ord-ec8a292568a8413b875f1e07643b965c
Source dataset
uspto-grants-2010_07
Patent number
US07763617B2

Reaction notes

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