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

HRID 1067917Notes

Reaction equation

HRID 1067917 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)malonateHCID 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 mixed 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. additionThe reaction mixed
  3. temperaturecooled
  4. stirringby stirring
  5. customthe aqueous layer was removed
  6. addition10% aqueous sodium chloride solution (210 mL) was added to the organic layer
  7. stirringwith stirring
  8. customthe aqueous layer was removed
  9. concentrationThe organic layer was concentrated
  10. dissolutionthe concentrated residue was dissolved in methanol (150 mL)
  11. temperatureunder heating
  12. temperatureThe reaction mixture was cooled to 10° C. or less
  13. stirringthe reaction mixture was stirred for 1 hr
  14. filtrationThe obtained crystals were collected by filtration
  15. washwashed with methanol (65 mL)

Sources & evidence

ORD record
ord-fce98318658f443f9bce0f9871f75410
Source dataset
uspto-grants-2001_06
Patent number
US06248897B1

Reaction notes

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