2-Aminophenol → 2-[4-Methyl-3-(trifluoromethyl)phenyl]-1,3-benzoxazole

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.

1. temperaturewas refluxed for 3 h
2. customThe excess thionyl chloride was removed in vacuo
3. dissolutionthe residue was dissolved in THF (20 mL)
4. additionit was added to
5. stirringThe resulting brownish mixture was stirred at rt for 3 h
6. customThe solvent was then removed
7. temperatureThe mixture was then refluxed for 3 h
8. temperaturethe mixture was cooled to rt
9. filtrationThe excess p-toluenesulfonic acid was filtered through Celite
10. customthe filtrate was evaporated to dryness
11. customThe crude was purified by flash chromatography on silica gel eluting with EtOAc:hexanes (1:9)

ORD record

ord-9546c37869f440218ad918dc8a6de1f1

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07087601B2