Diethyl Malonate → HCID 66885525, compound

HRID 905561Notes

Reaction equation

HRID 905561 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].Br[C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([F:25])[CH:23]=2)[N:18]=[CH:17][C:16]=1Cl.OS([O-])(=O)=O.[Na+]>O1CCOCC1>[CH2:12]([O:11][C:3](=[O:10])[CH:4]([C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([F:25])[CH:23]=2)[N:18]=[CH:17][CH:16]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:13]

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 516919Sodium BisulfateHCID 459257624-Bromo-3-chloro-6-fluoroquinoline

Product 1

HCID 66885525HCID 66885525, compoundYield 113.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a suspension of NaH (60% in oil dispersion, 2.2 g, 54 mmol) in 1,4-dioxane (26 mL) was added diethyl malonate (9 mL, 59 mmol). The reaction mixture was stirred at rt for 5 min and heated at 80° C. for 1 h. After cooling to rt, CuBr (1.0 g) and 4-bromo-3-chloro-6-fluoro-quinoline (5 g, 19.4 mmol) in dioxane (8 mL) were successively added. The mixture was stirred at 100° C. overnight. After cooling, 10% aq. NaHSO4 (100 mL) was added. The mixture was stirred 30 min. The two layers were decanted and the aq. layer was extracted three times with EA (3×150 mL). The combined org. layers were washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was triturated in DCM to yield the title compound as a yellow solid (6.71 g, 100% yield).

Workup

  1. temperatureheated at 80° C. for 1 h
  2. temperatureAfter cooling to rt
  3. stirringThe mixture was stirred at 100° C. overnight
  4. temperatureAfter cooling
  5. stirringThe mixture was stirred 30 min
  6. customThe two layers were decanted
  7. extractionthe aq. layer was extracted three times with EA (3×150 mL)
  8. washlayers were washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated to dryness
  12. customThe residue was triturated in DCM

Sources & evidence

ORD record
ord-16049609f29343fa9738c7ddcf09f9b0
Source dataset
uspto-grants-2011_09
Patent number
US08012961B2

Reaction notes

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