Diethyl acetylenedicarboxylate → HCID 59000764, compound

HRID 1594012Notes

Reaction equation

HRID 1594012 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[N:10]=[N:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:19]1([CH2:24]OS(C)(=O)=O)[CH2:23][CH2:22][CH2:21][CH2:20]1.[C:30]([C:37]([O:39][CH2:40][CH3:41])=[O:38])#[C:31][C:32]([O:34][CH2:35][CH3:36])=[O:33].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CC#N.C1COCC1.CCO>[CH2:40]([O:39][C:37]([C:30]1[C:31]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[C:24]([CH:19]2[CH2:20][CH2:21][CH2:22][CH2:23]2)[N:11]2[C:12]=1[C:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)=[CH:8][C:9]([N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)=[N:10]2)=[O:38])[CH3:41]

Participants

8

Reactant 4

HCID 69803Diethyl acetylenedicarboxylateHCID 2724141Tetrabutylammonium FluorideHCID 15712513Cyclopentylmethyl methanesulfonateHCID 69448414HCID 69448414, compound

Product 1

HCID 59000764HCID 59000764, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-(5-phenylpyridazin-3-yl)morpholine (150 mg, 0.622 mmol) and methanesulfonic acid cyclopentylmethyl ester (Newcomb et al. (1980) J. Org. Chem. 45:1707-1708) (890 mg, 4.99 mmol) in CH3CN (30 mL) was heated at reflux for 48 h. The solvent was removed in vacuo to provide a brown oil. Diethyl acetylenedicarboxylate (150 μL, 0.933 mmol) and a 1M solution of TBAF in THF (684 μL, 0.684 mmol) were added to a solution of this oil in THF (30 mL) and EtOH (5 mL). The reaction mixture was heated at reflux for 20 h. The solvent was removed in vacuo and the residue was purified by flash chromatography (silica gel, 15% EtOAc/hexane). The resulting residue was triturated in 1:1 Et2O/hexane to provide the title compound as an off-white solid. 1H NMR (DMSO-d6) δ 0.86 (t, J=7.1 Hz, 3H), 1.17 (t, J=7.1 Hz, 3H), 1.66 (m, 2H), 1.76 (m, 2H), 1.87 (m, 2H), 2.23 (m, 2H), 3.48 (m, 6H), 3.72 (m, 4H), 4.06 (m, 1H), 4.15 (q, J=7.1 Hz, 2H), 6.77 (s, 1H), 7.39 (m, 2H), 7.45 (m, 3H). Mass Spectrum (ESI+) m/e=492.3 (M+H).

Workup

  1. temperatureat reflux for 48 h
  2. customThe solvent was removed in vacuo
  3. customto provide a brown oil
  4. temperatureThe reaction mixture was heated
  5. temperatureat reflux for 20 h
  6. customThe solvent was removed in vacuo
  7. customthe residue was purified by flash chromatography (silica gel, 15% EtOAc/hexane)
  8. customThe resulting residue was triturated in 1:1 Et2O/hexane

Sources & evidence

ORD record
ord-9c37263facca4b229e4c65ce42b09e97
Source dataset
uspto-grants-2007_11
Patent number
US07300932B2

Reaction notes

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