Ethyl Acetate → 5,5-Dimethyl-3-phenyl-[1,2,4]oxadiazol-4-ylamine

HRID 339452Notes

Reaction equation

HRID 339452 reaction equation
[C:1](=[N:4][NH2:5])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[C:12](Cl)(=[N:19][OH:20])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(OCC)(=O)C>C(Cl)(Cl)Cl.C(Cl)Cl.O>[CH3:2][C:1]1([CH3:3])[O:20][N:19]=[C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:4]1[NH2:5]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 789372-Propanone, hydrazoneHCID 2756315N-hydroxybenzenecarboximidoyl chloride

Product 1

HCID 590166375,5-Dimethyl-3-phenyl-[1,2,4]oxadiazol-4-ylamineYield 40%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolvent3×HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

A solution of isopropylidene-hydrazine (0.59 g, 8 mmol) in 15 mL of chloroform and an aqueous solution of K2CO3 (0.5 g in 3 mL of water) were mixed and cooled in a 50 mL round-bottom flask chilled with ice water. A solution of benzohydroximoyl chloride (0.51 g, 3.2 mmol) in 10 mL of chloroform was added slowly with vigorous magnetic stirring. The ice batch was replaced with a 40° C. water bath and the mixture was stirred at 40° C. for 2 hours and then monitored by TLC (1:1 ethyl acetate:hexanes). When progression of the reaction began to significantly decelerate, the mixture was worked up by the addition of 10 mL of water and 60 mL of chloroform or methylene chloride. The organic layer was removed in a separatory funnel, dried over MgSO4, and the solvent removed on a rotary evaporator to yield a semi-solid. The crude product was triturated with 2% ether in hexanes (30 mL), by magnetic stirring in a round bottom flask or manipulating the material with a spatula. Filtration and air-drying provided 5,5-dimethyl-3-phenyl-[1,2,4]oxadiazol-4-ylamine in ca. 40% yield. 1H-NMR (300 MHz, CDCl3) δ (ppm): 7.77 (m, 2H), 7.48 (m, 3H), 3.4 (br), 1.55 (s, 6H).

Workup

  1. temperaturecooled in a 50 mL round-bottom flask
  2. customwas replaced with a 40° C.
  3. customThe organic layer was removed in a separatory funnel
  4. dry with materialdried over MgSO4
  5. customthe solvent removed on a rotary evaporator
  6. customto yield a semi-solid
  7. customThe crude product was triturated with 2% ether in hexanes (30 mL)
  8. stirringby magnetic stirring in a round bottom flask
  9. filtrationFiltration
  10. customair-drying

Sources & evidence

ORD record
ord-c7b1c5b60a8b4150816c39d5248eb77c
Source dataset
uspto-grants-2014_11
Patent number
US08895306B2

Reaction notes

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