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

HRID 1983082Notes

Reaction equation

HRID 1983082 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-f3d9dca0b88740958ba5af5e83fb257b
Source dataset
uspto-grants-2009_06
Patent number
US07541372B2

Reaction notes

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