Sodium hydride → 1-Tert-butyl 3-ethyl 2-(6-chloropyridazin-3-yl)malonate

HRID 1925132Notes

Reaction equation

HRID 1925132 reaction equation
[C:1]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[Cl:16][C:17]1[N:18]=[N:19][C:20](Cl)=[CH:21][CH:22]=1>O1CCOCC1>[Cl:16][C:17]1[N:18]=[N:19][C:20]([CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][C:10]([CH3:12])([CH3:11])[CH3:13])=[O:8])=[CH:21][CH:22]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 673313,6-DichloropyridazineHCID 96345tert-Butyl ethyl malonate

Product 1

HCID 592330361-Tert-butyl 3-ethyl 2-(6-chloropyridazin-3-yl)malonateYield 143.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

tert-Butyl ethyl malonate (41.3 ml, 211 mmol) was added drop-wise to a suspension of sodium hydride (19.33 g, 483 mmol) in dioxane (1000 mL) at 0° C. The reaction was stirred at 0° C. for 1 hr and then allowed to warm to ambient temperature. 3,6-dichloropyridazine (30 g, 201 mmol) was then added portion wise at 25° C. The reaction was stirred at reflux for 2 hrs and then solvent was removed via rotary evaporation. The resulting residue was dissolved in EtOAc (400 mL), and the organic phase was washed with saturated NaHCO3 (400 mL), dried over MgSO4, filtered, and concentrated to dryness via rotary evaporation. This reaction was repeated. The combined crude residues from both batches was purified via MPLC (Hex:EtOAc, 8:2) to provide the title compound, 1-tert-butyl 3-ethyl 2-(6-chloropyridazin-3-yl)malonate (86.5 g, 288 mmol, 71.3%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.12-1.23 (m, 3 H) 1.36-1.52 (m, 9 H) 4.20 (m, J=10.71, 7.22, 7.22, 3.85, 3.85 Hz, 2 H) 5.29 (s, 1 H) 7.85 (d, J=8.84 Hz, 1 H) 7.99 (d, J=8.84 Hz, 1 H). ESI-MS:m/z 301.2 (M+H)+.

Workup

  1. temperatureto warm to ambient temperature
  2. stirringThe reaction was stirred
  3. temperatureat reflux for 2 hrs
  4. customsolvent was removed via rotary evaporation
  5. dissolutionThe resulting residue was dissolved in EtOAc (400 mL)
  6. washthe organic phase was washed with saturated NaHCO3 (400 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness via rotary evaporation
  10. customwas purified via MPLC (Hex:EtOAc, 8:2)

Sources & evidence

ORD record
ord-afa7c482c5d34a94a9a1163299142ab1
Source dataset
uspto-grants-2012_05
Patent number
US08178534B2

Reaction notes

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