Ethyl Acetate → 1,2-Benzisoxazole

HRID 2381221Notes

Reaction equation

HRID 2381221 reaction equation
CCOC(C)=O.[CH3:7][C:8]1[CH:9]=[CH:10][C:11](S(O)(=O)=O)=[CH:12][CH:13]=1.O.[O:19]1C=CC=[N:20]1.[F-].[K+]>O>[O:19]1[C:13]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[CH:7]=[N:20]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 9254IsoxazoleHCID 521998p-Toluenesulfonic acid monohydrateHCID 522689Potassium Fluoride

Product 1

HCID 710731,2-Benzisoxazole

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

To a 100 L cylindrical vessel with heating coils were charged EtOAc (20 L) and TsOH/H2O (2.304 kg, 12.11 mol), and the mixture was heated to 35-45° C. to dissolve. The acid solution was fed into the isoxazole batch with further distilling, maintaining a constant volume of 25 L. An additional 20 L of EtOAc was distilled to azeotropically dry the mixture. A slurry began to form, and it continued to thicken on addition and concentration. The final KF was 400 ppm water. The batch was heated to 60° C. and allowed to slowly cool to ambient temperature overnight.

Workup

  1. dissolutionto dissolve
  2. temperaturemaintaining a constant volume of 25 L
  3. distillationAn additional 20 L of EtOAc was distilled
  4. customto azeotropically dry the mixture
  5. customto form
  6. additionto thicken on addition and concentration
  7. temperatureThe batch was heated to 60° C.
  8. temperatureto slowly cool to ambient temperature overnight

Sources & evidence

ORD record
ord-44ee286526f14510a4e56e0f15e3fcc1
Source dataset
uspto-grants-2012_09
Patent number
US08258161B2

Reaction notes

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