Diethyl methylmalonate → HCID 59233051, compound

HRID 1925149Notes

Reaction equation

HRID 1925149 reaction equation
[H-].[Na+].[CH3:3][CH:4]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]([O:7][CH2:8][CH3:9])=[O:6].[Cl:15][C:16]1[N:17]=[N:18][C:19](Cl)=[CH:20][CH:21]=1>O1CCOCC1>[Cl:15][C:16]1[N:17]=[N:18][C:19]([C:4]([CH3:3])([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 11857Diethyl methylmalonateHCID 24758Sodium hydrideHCID 673313,6-Dichloropyridazine

Product 1

HCID 59233051HCID 59233051, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of NaH (13.42 g, 336 mmol) in dioxane (800 mL) was added diethyl 2-methylmalonate (42.9 ml, 252 mmol) drop-wise at 0° C. The reaction was stirred at 0° C. for 1 hr and allowed to warm to ambient temperature. 3,6-dichloropyridazine (25 g, 168 mmol) was then added portion-wise at 25° C. The reaction was then stirred at reflux for 1 hr. Solvent was removed via rotary evaporation and the resulting residue was dissolved in EtOAc. The organic solution was washed with saturated NaHCO3 (100 mL) followed by 5% citric acid. The organic layer was then dried with MgSO4, filtered, and concentrated to dryness. The resulting residue was purified via MPLC (Hex:EtOAc, 3:1) to provide the title compound, diethyl 2-(6-chloropyridazin-3-yl)-2-methylmalonate 48A (12 g, 25% yield) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.18 (s, 6 H) 1.81 (s, 3H) 4.21 (dd, J=7.07, 2.27 Hz, 4 H) 8.00 (s, 2 H). ESI-MS:m/z 287.1 (M+H)+.

Workup

  1. temperatureto warm to ambient temperature
  2. stirringThe reaction was then stirred
  3. temperatureat reflux for 1 hr
  4. customSolvent was removed via rotary evaporation
  5. dissolutionthe resulting residue was dissolved in EtOAc
  6. washThe organic solution was washed with saturated NaHCO3 (100 mL)
  7. dry with materialThe organic layer was then dried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe resulting residue was purified via MPLC (Hex:EtOAc, 3:1)

Sources & evidence

ORD record
ord-04fbb768e6f44c2a9fd87ef0aca5f5f3
Source dataset
uspto-grants-2012_05
Patent number
US08178534B2

Reaction notes

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