Hydrochloric Acid → 5-Chloro-1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carbaldehyde

Temperature

0 °C

DMF (106 mL) was stirred under N2 while cooling in an ice/salt bath to 0° C. POCl3 (364 mL) was added dropwise at a rate such that the temperature did not rise above 10° C. The mixture was then stirred at 0° C. briefly and 5-hydroxy-1-methyl-3-(trifluoromethyl)-1H-pyrazole (106 g) was added with constant stirring. The mixture was stirred while slowly heating to 90° C. As the temperature approached 90° C. the reaction became exothermic and HCl gas evolved. The temperature rose to reflux. After the exotherm subsided the mixture was heated at gentle reflux for 16 h. The dark amber solution was cooled to RT and then poured onto 3 kg ice with stirring. The mixture was mixed thoroughly with the ice and more ice added to maintain the temperature below 5° C. The resulting slurry was stirred continuously for 4 h with occasional addition of ice to maintain low temperature. The solid was separated from the liquid phase by drawing the aqueous phase through a sintered glass filter tube. The solid was reslurried with water (4×1 L) and then collected by filtration and air dried. The product was recrystallized from hexane which gave the desired compound as white needles (137 g). m.p. 39-41° C. An additional 30 g product was obtained by concentration of the mother liquor.

1. customdid not rise above 10° C
2. stirringThe mixture was stirred
3. temperaturewhile slowly heating to 90° C
4. customapproached 90° C.
5. temperatureto reflux
6. temperaturewas heated
7. temperatureat gentle reflux for 16 h
8. temperatureThe dark amber solution was cooled to RT
9. stirringwith stirring
10. additionadded
11. temperatureto maintain the temperature below 5° C
12. stirringThe resulting slurry was stirred continuously for 4 h with occasional addition of ice
13. temperatureto maintain low temperature
14. customThe solid was separated from the liquid phase
15. filtrationfilter tube
16. filtrationcollected by filtration and air
17. customdried
18. customThe product was recrystallized from hexane which

ORD record

ord-c46a6614cec04322a0499d46d6b1c628

Source dataset

uspto-grants-1993_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05223526