Phosphorus oxychloride → 2-Chloro-4-[4-(trifluoromethyl)phenyl]-1,3-thiazole

A mixture of 28.05 g (114.4 mmole) of 4-(4-trifluoromethyl-phenyl)-3H-thiazol-2-one and 85 mL (0.92 mole) of phosphorus oxychloride was heated at reflux for 5 hours. The mixture was cooled and the excess phosphorus oxychloride was removed under reduced pressure. The residue was diluted with ethyl acetate and the slurry was poured onto ice. The mixture was made basic by the addition of saturated aqueous sodium carbonate solution. The ethyl acetate layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with ethyl acetate-hexanes (gradient 10:90-20:80) to give 19.34 g of 2-chloro-4-(4-trifluoromethyl-phenyl)-thiazole as a light brown solid.

1. temperaturewas heated
2. temperatureat reflux for 5 hours
3. temperatureThe mixture was cooled
4. customthe excess phosphorus oxychloride was removed under reduced pressure
5. additionThe residue was diluted with ethyl acetate
6. additionthe slurry was poured onto ice
7. additionThe mixture was made basic by the addition of saturated aqueous sodium carbonate solution
8. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by silica gel chromatography
12. washeluting with ethyl acetate-hexanes (gradient 10:90-20:80)

ORD record

ord-c9a71fe1ce7a4dfeb8d6497345fa9dca

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08044213B2