Benzenecarboximidic acid, ethyl ester, hydrochloride (1:1) → 2-(5-Methyl-3-phenyl-isoxazol-4-yl)-5-phenyl-[1,3,4]oxadiazole

HRID 2421091Notes

Reaction equation

HRID 2421091 reaction equation
Cl.[C:2](=N)(OCC)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[O-]CC.[Na+].[CH3:17][C:18]1[O:22][N:21]=[C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:19]=1[C:29]([NH:31][NH2:32])=[O:30]>C(O)C.O1CCOCC1>[CH3:17][C:18]1[O:22][N:21]=[C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:19]=1[C:29]1[O:30][C:2]([C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)=[N:32][N:31]=1

Participants

6

Reactant 3

HCID 79249Benzenecarboximidic acid, ethyl ester, hydrochloride (1:1)HCID 7279245-Methyl-3-phenyl-4-isoxazolecarbohydrazideHCID 2723922Sodium ethoxide

Product 1

HCID 167225322-(5-Methyl-3-phenyl-isoxazol-4-yl)-5-phenyl-[1,3,4]oxadiazoleYield 58.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
180 °C

Procedure

To a solution of ethyl benzimidate hydrochloride (376 mg; 2.03 mmol) in ethanol (4 mL) was added at 0° C. sodium ethoxide (2.72 M in ethanol, 355 L, 0.99 mmol) and stirred for 15 min. The suspension was filtered off and 5-methyl-3-phenyl-isoxazole-4-carboxylic acid hydrazide (200 mg, 0.92 mmol) was added and stirred for 90 h at 70° C. The reaction mixture was suspended in dioxane (4 mL) and heated in the microwave for 30 min at 180° C. Concentration and then purification by chromatography (SiO2, heptane:ethyl acetate=95:5 to 60:40) afforded the title compound (163 mg, 29%) as a white solid. MS: m/e=304.2 [M+H]+.

Workup

  1. filtrationThe suspension was filtered off
  2. stirringstirred for 90 h at 70° C
  3. concentrationConcentration
  4. custompurification by chromatography (SiO2, heptane:ethyl acetate=95:5 to 60:40)

Sources & evidence

ORD record
ord-fe6219d3faba43e1aab7b2a71187a38f
Source dataset
uspto-grants-2011_06
Patent number
US07956074B2

Reaction notes

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