Sodium borohydride → Diethyl 4-(4-chloro-2-aminobenzoyl)-1H-pyrazole-3,5-dicarboxylate

Temperature

8 °C

Alternatively, the title compound can be prepared as follows: A mixture of nickel acetate (444 g, 1.78 moles) and water (6.6 L) was cooled to 8° C. with stirring under nitrogen: then a solution of sodium borohydride (271 g, 7.16 moles) in water (3.55 L) was added dropwise over 1.5 hours maintaining the reaction temperature between 8° C. and 12° C. The reaction mixture was then stirred for 1.5 hours at 8-12° C. The reaction mixture was filtered through a coarse scintered glass filter funnel, keeping, the black filter cake wet (Caution: this black powder may be pyrophoric if allowed to dry). The filter cake was washed first with water (6×2 L), then with ethanol (2×2 L) and finally with methanol (1 L). The methanol wet filter cake (Ni2B, pyrophoric) was transferred to a 22 L flask with methanol (8 L). A solution of diethyl 4-(4-chloro-2-nitrobenzoyl)-1H-pyrazole-3,5-dicarboxylate (111.0 g, 0.28 mole) in hydrochloric acid (2.52 L) was added. The reaction mixture was heated to 64° C. and was kept at 64° C. for 6 hours; then was allowed to cool to room temperature and was filtered through CELITE™. The CELITE™ layer was washed with methanol (2×2 L). The filtrate and wash liquors were combined and the methanol was distilled off under water aspirator vacuum. Water (1 L) was added to the reaction and the mixture was filtered. The filter cake was washed with water (2×500 mL) and dried under vacuum at 40° C. to give the title compound as a yellowish solid (98.81 g, 96%).

1. temperaturemaintaining the reaction temperature between 8° C. and 12° C
2. stirringThe reaction mixture was then stirred for 1.5 hours at 8-12° C
3. filtrationThe reaction mixture was filtered through a coarse scintered glass
4. filtrationfilter funnel
5. customto dry)
6. washThe filter cake was washed first with water (6×2 L)
7. customThe methanol wet filter cake (Ni2B, pyrophoric) was transferred to a 22 L flask with methanol (8 L)
8. temperatureThe reaction mixture was heated to 64° C.
9. temperatureto cool to room temperature
10. filtrationwas filtered through CELITE™
11. washThe CELITE™ layer was washed with methanol (2×2 L)
12. washThe filtrate and wash liquors
13. distillationthe methanol was distilled off under water
14. additionWater (1 L) was added to the reaction
15. filtrationthe mixture was filtered
16. washThe filter cake was washed with water (2×500 mL)
17. customdried under vacuum at 40° C.

ORD record

ord-3e4d0e937696433a8cd111079ac62962

Source dataset

uspto-grants-2000_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06124281