Acetone → 3-(4-Chloro-3-trifluoromethylphenyloxy)-5-methylpyrazole

3-(4-Amino-3-trifluoromethylphenyloxy)-5-methylpyrazole (2.00 g, 7.8 mmol) was added to a mixed solution of concentrated hydrochloric acid (2.1 ml) and acetone (20 ml) at room temperature, and the mixture was stirred at room temperature for 20 minutes. After the mixture was cooled below 0° C., a solution of sodium nitrite (0.54 g, 7.8 mmol) in water (3 ml) was dropwise added, and the mixture was stirred at an ambient temperature for 30 minutes. Then, cuprous chloride (0.85 g, 8.6 mmol) was little by little added at 0° C., and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, the reaction mixture was poured into 1N hydrochloric acid (50 ml) and extracted with ethyl acetate (50 ml×2). An organic layer was washed with water (50 ml×3), dried over anhydrous magnesium sulfate and filtered to remove a desiccant, and the solvent was distilled off from the filtrate under reduced pressure. The resultant crude product was purified with a silica gel column (ethyl acetate/hexane=1/3), to give a yellowish viscous substance of 3-(4-chloro-3-trifluoromethylphenyloxy)-5-methylpyrazole (2.12 g, yield: 98.7%). 1H-NMR (CDCl3, TMS, ppm): δ 2.25 (s, 3H), 5.64 (s, 1H), 7.23 (dd, J=3.0 and 8.8 Hz, 1H), 7.31-7.46 (m, 2H), 10.56 (br s, 1H).

1. temperatureAfter the mixture was cooled below 0° C.
2. stirringthe mixture was stirred at an ambient temperature for 30 minutes
3. additionby little added at 0° C.
4. stirringthe mixture was stirred at room temperature for 1 hour
5. customAfter completion of the reaction
6. extractionextracted with ethyl acetate (50 ml×2)
7. washAn organic layer was washed with water (50 ml×3)
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. customto remove a desiccant, and the solvent
11. distillationwas distilled off from the filtrate under reduced pressure
12. customThe resultant crude product was purified with a silica gel column (ethyl acetate/hexane=1/3)

ORD record

ord-4a243b8508a845d48e6462855a55b6f0

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07700786B2