Toluene → Dimethyl [4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzylidene]-malonate

HRID 47910Notes

Reaction equation

HRID 47910 reaction equation
CS([O:5][CH2:6][CH2:7][C:8]1[N:9]=[C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[O:11][C:12]=1[CH3:13])(=O)=O.O[C:21]1[CH:36]=[CH:35][C:24]([CH:25]=[C:26]([C:31]([O:33][CH3:34])=[O:32])[C:27]([O:29][CH3:30])=[O:28])=[CH:23][CH:22]=1.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[CH3:13][C:12]1[O:11][C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[N:9][C:8]=1[CH2:7][CH2:6][O:5][C:21]1[CH:36]=[CH:35][C:24]([CH:25]=[C:26]([C:31]([O:33][CH3:34])=[O:32])[C:27]([O:29][CH3:30])=[O:28])=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 103565Dimethyl ((4-hydroxyphenyl)methylene)malonate2×HCID 105407732-(5-Methyl-2-phenyl-1,3-oxazol-4-yl)ethyl methanesulfonate2×

Product 1

HCID 10788309Dimethyl [4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzylidene]-malonateYield 85%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

2-(5-Methyl-2-phenyl-4-oxazolyl)ethyl methanesulfonate obtained in Example 4 (compound [7]; 24.4 g) and dimethyl 2-(4-hydroxybenzylidene)-malonate obtained in Preparation Example 1 (compound [8]; 20.5 g) were mixed with tetrabutylammonium bromide (1.4 g) and toluene (210 mL). The mixture was heated to 90° C. and dissolved. Then potassium carbonate (13.2 g) was added and the mixture was stirred at 110° C. for 6 hr. The reaction mixture was ice-cooled and water (210 mL) was added, which was followed by stirring. After standing still, the aqueous layer was removed and 10% aqueous sodium chloride solution (210 mL) was added to the organic layer with stirring. The reaction mixture was allowed to stand and the aqueous layer was removed. The organic layer was concentrated and the concentrated residue was dissolved in methanol (150 mL) under heating. The reaction mixture was cooled to 10° C. or less and the reaction mixture was stirred for 1 hr. The obtained crystals were collected by filtration and washed with methanol (65 mL) to give the title compound (compound [9]; 31.1 g, yield 85.0%).

Workup

  1. dissolutiondissolved
  2. temperaturecooled
  3. stirringby stirring
  4. customthe aqueous layer was removed
  5. addition10% aqueous sodium chloride solution (210 mL) was added to the organic layer
  6. stirringwith stirring
  7. customthe aqueous layer was removed
  8. concentrationThe organic layer was concentrated
  9. dissolutionthe concentrated residue was dissolved in methanol (150 mL)
  10. temperatureunder heating
  11. temperatureThe reaction mixture was cooled to 10° C. or less
  12. stirringthe reaction mixture was stirred for 1 hr
  13. filtrationThe obtained crystals were collected by filtration
  14. washwashed with methanol (65 mL)

Sources & evidence

ORD record
ord-21fb21a7fe0d432d851df1992dd4eecb
Source dataset
uspto-grants-2004_03
Patent number
US06699996B2

Reaction notes

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