1,2-Dichloroethane → 5-(4,5-Diphenylisoxazol-3-yl)-3-(4-methyl-2-(trifluoromethyl)phenyl)-1,2,4-oxadiazole

HRID 1804522Notes

Reaction equation

HRID 1804522 reaction equation
[C:1]1([C:7]2[C:8]([C:18](O)=O)=[N:9][O:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[OH:35][N:36]=[C:37]([NH2:49])[C:38]1[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][C:39]=1[C:45]([F:48])([F:47])[F:46]>CN(C)C=O>[C:1]1([C:7]2[C:8]([C:18]3[O:35][N:36]=[C:37]([C:38]4[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][C:39]=4[C:45]([F:47])([F:46])[F:48])[N:49]=3)=[N:9][O:10][C:11]=2[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 585372184,5-Diphenylisoxazole-3-carboxylic acidHCID 86659950HCID 86659950, compound

Product 1

HCID 674577985-(4,5-Diphenylisoxazol-3-yl)-3-(4-methyl-2-(trifluoromethyl)phenyl)-1,2,4-oxadiazoleYield 29.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 2 dram reaction vial containing a stir bar was charged with 4,5-diphenylisoxazole-3-carboxylic acid (17-B, 48.6 mg, 0.183 mmol), EDC (43.9 mg, 0.229 mmol), HOBT (35.1 mg, 0.229 mmol), and dimethylformamide (1 mL). The vial was flushed with dry nitrogen, sealed, and the reaction was stirred at room temperature for 30 minutes. N′-Hydroxy-4-methyl-2-(trifluoromethyl)benzimidamide (40.0 mg, 0.183 mmol) was introduced. The vial was flushed with dry nitrogen, sealed, stirred at room temperature for 30 minutes, and then placed on a reactor block set to 60° C. overnight. Water was added dropwise (−0.5 mL) until the solution remained cloudy, and then the reaction was cooled to room temperature. Additional water (5 mL) was added after cooling, and the reaction was placed in a sonicator bath for 60 min. A gummy solid formed on the side of the flask and stir bar. The aqueous solution was decanted and the residue washed with water and then partially dried under a stream of air. The gummy solid was dissolved in methanol (1-2 mL), transferred, and evaporated to dryness to give a pale yellow solid The pale yellow solid was purified by flash chromatography (12 g Isco silica gel). Elution with dichloromethane afforded the major product. The product containing fractions were evaporated to afford 5-(4,5-diphenylisoxazol-3-yl)-3-(4-methyl-2-(trifluoromethyl)phenyl)-1,2,4-oxadiazole (24 mg) MS M+1=448.1.

Workup

  1. customA 2 dram reaction
  2. additionvial containing a stir bar
  3. customThe vial was flushed with dry nitrogen
  4. customsealed
  5. customThe vial was flushed with dry nitrogen
  6. customsealed
  7. stirringstirred at room temperature for 30 minutes
  8. customplaced on a reactor
  9. waitblock set to 60° C. overnight
  10. additionWater was added dropwise (−0.5 mL) until the solution
  11. temperaturethe reaction was cooled to room temperature
  12. additionAdditional water (5 mL) was added
  13. temperatureafter cooling
  14. waitthe reaction was placed in a sonicator bath for 60 min
  15. customA gummy solid formed on the side of the flask
  16. stirringstir bar
  17. customThe aqueous solution was decanted
  18. washthe residue washed with water
  19. custompartially dried under a stream of air
  20. dissolutionThe gummy solid was dissolved in methanol (1-2 mL)
  21. customevaporated to dryness
  22. customto give a pale yellow solid The pale yellow solid
  23. customwas purified by flash chromatography (12 g Isco silica gel)
  24. washElution with dichloromethane
  25. customafforded the major product
  26. additionThe product containing fractions
  27. customwere evaporated

Sources & evidence

ORD record
ord-9ed1f5f61c1a4c1d9e600f44ac82837d
Source dataset
uspto-grants-2013_01
Patent number
US08354398B2

Reaction notes

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