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

HRID 1925132ノート

反応式

HRID 1925132 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
0 °C

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-afa7c482c5d34a94a9a1163299142ab1
出典データセット
uspto-grants-2012_05
特許番号
US08178534B2

反応ノート

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