Hydrochloric Acid → Oxazole, 4,5-dimethyl-2-[4-(trifluoromethyl)phenyl]-, 3-oxide

HRID 1160282Notes

Reaction equation

HRID 1160282 reaction equation
[CH3:1][C:2](=[N:6][OH:7])[C:3](=[O:5])[CH3:4].[F:8][C:9]([F:19])([F:18])[C:10]1[CH:17]=[CH:16][C:13]([CH:14]=O)=[CH:12][CH:11]=1.Cl.O1CCOCC1>C(OCC)C.C(O)(=O)C>[CH3:1][C:2]1[N+:6]([O-:7])=[C:14]([C:13]2[CH:12]=[CH:11][C:10]([C:9]([F:8])([F:18])[F:19])=[CH:17][CH:16]=2)[O:5][C:3]=1[CH3:4]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 679964-(Trifluoromethyl)benzaldehydeHCID 63989692-Oxime 2,3-butanedione

Product 1

HCID 10515280Oxazole, 4,5-dimethyl-2-[4-(trifluoromethyl)phenyl]-, 3-oxideYield 35%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

A 100 mL pear-shaped flask was charged with butane-2,3-dione monooxime (2.1 g, 20.4 mmol), 4-(trifluoromethyl)benzaldehyde (3.0 mL, 22.4 mmol), and acetic acid (20 mL). The mixture was cooled to 0° C. A solution of 4N HCl in dioxane (7.0 mL, 28.0 mmol) was added dropwise to the reaction and the resultant mixture was stirred at 0° C. for 20 minutes. Diethyl ether (30 mL) was added to the reaction and the mixture was allowed to warm to room temperature overnight. The solvent was removed under reduced pressure and the resulting residue was taken up in water (300 mL). Conc. NH4OH(aq) was added to adjust the pH to 9.0. The mixture was extracted with ethyl acetate (2×75 mL), and the combined organic layers were washed with water (100 mL), followed by saturated brine (100 mL). The organic layer was dried (Na2SO4) and the solvent removed under reduced pressure. The resulting residue was purified via radial chromatography (3% MeOH in DCM) to yield 1.8 g (35%) of 4,5-dimethyl-2-(4-trifluoromethyl-phenyl)-oxazole-3-oxide as a white solid. LC/MSD m/e: 258.1 (M+H); 1H NMR (400 MHz) (Acetone-d6) δ 8.68 (d, 2H, J=8.0 Hz), 7.89 (d, 2H, J=8.0 Hz), 2.45 (s, 3H), 2.16 (s, 3H).

Workup

  1. temperatureto warm to room temperature overnight
  2. customThe solvent was removed under reduced pressure
  3. additionConc. NH4OH(aq) was added
  4. extractionThe mixture was extracted with ethyl acetate (2×75 mL)
  5. washthe combined organic layers were washed with water (100 mL)
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. customthe solvent removed under reduced pressure
  8. customThe resulting residue was purified via radial chromatography (3% MeOH in DCM)

Sources & evidence

ORD record
ord-5dbf536b77524b89969e79bbe7ad148a
Source dataset
uspto-grants-2010_10
Patent number
US07816367B2

Reaction notes

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