Reaktion #7788

Reaktionsgleichung

p-toluenesulfonic acid

4-methyl-3-(trifluoromethyl)benzoic acid

thionyl chloride

2-aminophenol

diisopropylethylamine

→

2-[4-methyl-3-(trifluoromethyl)phenyl]-1,3-benzoxazole

Lösungsmittel

toluene

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas refluxed for 3 h
2. 2
   SonstigeThe excess thionyl chloride was removed in vacuo
3. 3
   workup.DISSOLUTIONthe residue was dissolved in THF (20 mL)
4. 4
   workup.ADDITIONit was added to
5. 5
   workup.STIRRINGThe resulting brownish mixture was stirred at rt for 3 h
6. 6
   SonstigeThe solvent was then removed
7. 7
   TemperaturThe mixture was then refluxed for 3 h
8. 8
   Temperaturthe mixture was cooled to rt
9. 9
   FiltrationThe excess p-toluenesulfonic acid was filtered through Celite
10. 10
    Sonstigethe filtrate was evaporated to dryness
11. 11
    SonstigeThe crude was purified by flash chromatography on silica gel eluting with EtOAc:hexanes (1:9)

Vorschrift

A mixture of 4-methyl-3-(trifluoromethyl)benzoic acid (1.0 g, 4.9 mmol) and thionyl chloride (15 mL) was refluxed for 3 h and then stirred at rt overnight. The excess thionyl chloride was removed in vacuo, the residue was dissolved in THF (20 mL), and it was added to a cooled (0° C.) solution of 2-aminophenol (0.53 g, 4.9 mmol) and diisopropylethylamine (1.0 mL, 5.9 mmol) in anhydrous THF (15 mL). The resulting brownish mixture was stirred at rt for 3 h. The solvent was then removed and p-toluenesulfonic acid (3.7 g, 19.6 mmol) and toluene (20 mL) were added to the dark oil. The mixture was then refluxed for 3 h and the mixture was cooled to rt. The excess p-toluenesulfonic acid was filtered through Celite and the filtrate was evaporated to dryness. The crude was purified by flash chromatography on silica gel eluting with EtOAc:hexanes (1:9) to afford 2-[4-methyl-3-(trifluoromethyl)phenyl]-1,3-benzoxazole as a colorless solid.

Quelle