2-Methylbenzoic acid → 2-(5-Methyl-3-phenyl-isoxazol-4-yl)-5-o-tolyl-[1,3,4]oxadiazole

HRID 2421092Notes

Reaction equation

HRID 2421092 reaction equation
[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[C:13]([NH:15][NH2:16])=[O:14].P(Cl)(Cl)(Cl)=O.[C:22]1([CH3:31])[C:23]([C:28](O)=O)=[CH:24][CH:25]=[CH:26][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C>[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[C:13]1[O:14][C:31]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH3:28])=[N:16][N:15]=1

Participants

6

Reactant 4

HCID 83732-Methylbenzoic acidHCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 7279245-Methyl-3-phenyl-4-isoxazolecarbohydrazide

Product 1

HCID 167225332-(5-Methyl-3-phenyl-isoxazol-4-yl)-5-o-tolyl-[1,3,4]oxadiazoleYield 34%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 5-methyl-3-phenyl-isoxazole-4-carboxylic acid hydrazide (200 mg, 0.92 mmol) in phosphorus oxychloride (1.68 mL, 18.4 mmol) was added o-toluic acid (188 mg, 1.38 mmol) and was stirred for 30 min at ambient temperature. The suspension was heated for 2 h at 90° C. whereupon it became homogeneous. After cooling to ambient temperature it was then poured onto a mixture of ethyl acetate (20 mL) and aqueous sodium carbonate (saturated, 20 mL). The aqueous phase was then separated and extracted with ethyl acetate (20 mL). The combined organic extracts were then washed with aqueous sodium carbonate and brine. Concentration and trituration in tert-butylmethylether (3 mL) afforded the title compound (99 mg, 34%) as a white solid. MS: m/e=318.1 [M+H]+.

Workup

  1. temperatureThe suspension was heated for 2 h at 90° C. whereupon it
  2. temperatureAfter cooling to ambient temperature it
  3. customThe aqueous phase was then separated
  4. extractionextracted with ethyl acetate (20 mL)
  5. washThe combined organic extracts were then washed with aqueous sodium carbonate and brine
  6. concentrationConcentration and trituration in tert-butylmethylether (3 mL)

Sources & evidence

ORD record
ord-bad400e52c504241a270acbb64c5e541
Source dataset
uspto-grants-2011_06
Patent number
US07956074B2

Reaction notes

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