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

HRID 1925132노트

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HRID 1925132 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
0 °C

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-afa7c482c5d34a94a9a1163299142ab1
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08178534B2

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