反应详情

温度

0 °C

To a stirred concentrated H2SO4 (473 mL) was added NaNO2 (81.63 g, 1.18 mol, 1.20 eq.) at 0˜5° C. in several portions. Then the mixture was heated to 45˜50° C. and stirred at this temperature for 1 hour. This acid mixture was cooled to 0° C. and reserved to use in the next step. To a solution of 2-chloro-6-fluoro-4-trifluoromethylaniline (210 g, 985.9 mmol) in acetic acid (1.05 L) was added concentrated H2SO4 (44.45 mL) at rt. Then the solution was added dropwise to the above H2SO4—NaNO2 mixture at 0° C. Then the mixture was heated to 50° C. After stirring for 1 hour, this reaction mixture was added to a suspension of 1,2-dicyano-3-hydroxyprop-2-ene (224 g, 1.48 mol, 1.5 eq.) and anhydrous sodium acetate (1.68 kg, 20.4 mol, 13.78 eq.) in H2O (1.05 L) at 5˜10° C. After stirring for 1 hour, this reaction mixture was diluted with water and extracted with dichloromethane (DCM). The organic layers were stirred vigorously with 30% ammonium hydroxide solution overnight. The organic phase separated, dried over anhydrous Na2SO4, filtered and concentrated under vacuum to give yellow solid. The solid was recrystallized from ethyl acetate (EA) to afford 5-amino-1-(2-chloro-6-fluoro-4-(trifluoromethyl)-phenyl)-1H-pyrazole-3-carbonitrile as yellow solid (220 g, 73%).

1. temperatureThen the mixture was heated to 45˜50° C.
2. temperatureThen the mixture was heated to 50° C
3. stirringAfter stirring for 1 hour
4. stirringAfter stirring for 1 hour
5. extractionextracted with dichloromethane (DCM)
6. stirringThe organic layers were stirred vigorously with 30% ammonium hydroxide solution overnight
7. customThe organic phase separated
8. dry with materialdried over anhydrous Na2SO4
9. filtrationfiltered
10. concentrationconcentrated under vacuum
11. customto give yellow solid
12. customThe solid was recrystallized from ethyl acetate (EA)