Methyl acetoacetate → Methyl (E)-7-[2,6-diisopropyl-4-(4-fluorophenyl)-5-methoxyiminomethyl-pyrid-3-yl]-5-hydroxy-3-oxo-hept-6-enoate

HRID 2081272Notes

Reaction equation

HRID 2081272 reaction equation
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.[CH:16]([C:19]1[C:24](/[CH:25]=[CH:26]/[CH:27]=[O:28])=[C:23]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[C:22]([CH:36]=[N:37][O:38][CH3:39])=[C:21]([CH:40]([CH3:42])[CH3:41])[N:20]=1)([CH3:18])[CH3:17]>O1CCCC1.CCCCCC.O.C(O)(=O)C>[CH:16]([C:19]1[C:24](/[CH:25]=[CH:26]/[CH:27]([OH:28])[CH2:5][C:3](=[O:4])[CH2:2][C:1]([O:7][CH3:8])=[O:6])=[C:23]([C:29]2[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=2)[C:22]([CH:36]=[N:37][O:38][CH3:39])=[C:21]([CH:40]([CH3:42])[CH3:41])[N:20]=1)([CH3:17])[CH3:18]

Participants

9

Reactant 4

HCID 7757Methyl acetoacetateHCID 24758Sodium hydrideHCID 86746531(E)-3-[2,6-diisopropyl-4-(4-fluorophenyl)-5-methoxyiminomethyl-pyrid-3-yl]-prop-2-enalHCID 178418339Butyllithium

Product 1

HCID 86746532Methyl (E)-7-[2,6-diisopropyl-4-(4-fluorophenyl)-5-methoxyiminomethyl-pyrid-3-yl]-5-hydroxy-3-oxo-hept-6-enoate

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Procedure

0.18 ml (1.65 mmol) of methyl acetoacetate in 5 ml of dry tetrahydrofuran are added dropwise at -5° C. under nitrogen to a suspension of 67 mg (2.2 mmol) of 80% pure sodium hydride in 10 ml of dry tetrahydrofuran. After 15 min, 1.01 ml (1.65 mmol) of 15% strength butyllithium in n-hexane are added dropwise at the same temperature and the mixture is then stirred for 15 minutes. 410 mg (1.1 mmol) of the compound from Example 4, dissolved in 10 ml of dry tetrahydrofuran, are then added and the mixture is stirred at -5° C. for 30 minutes. 0.3 ml of glacial acetic acid is cautiously added to the reaction solution, it is diluted with 100 ml of water and the mixture is extracted 3 times with 100 ml of ether each time. The combined organic phases are washed twice with saturated sodium hydrogencarbonate solution, dried over magnesium sulphate and concentrated in vacuo. The residue is filtered through silica gel (solvent: ethyl acetate/ petroleum ether 1:1).

Workup

  1. additionare then added
  2. stirringthe mixture is stirred at -5° C. for 30 minutes
  3. extractionthe mixture is extracted 3 times with 100 ml of ether each time
  4. washThe combined organic phases are washed twice with saturated sodium hydrogencarbonate solution
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated in vacuo
  7. filtrationThe residue is filtered through silica gel (solvent: ethyl acetate/ petroleum ether 1:1)

Sources & evidence

ORD record
ord-2870c8ba58b44492bd9a73f04f6ba837
Source dataset
uspto-grants-1993_02
Patent number
US05183897

Reaction notes

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