Acetic Acid → 4-Nitroindazole

Temperature

17.5 °C

A mixture of 2-methyl-3-nitro aniline (200 g, 1.315 moles), acetic acid (8000 ml) was cooled to 15-20° C. and a solution of sodium nitrite (90.6 g, 1.315 moles) in water (200 ml) was slowly added over 30 min. After the addition, the reaction temp. was increased to 25-30° C. and the reaction was stirred at this temp for 2-3 h. Reaction progress was monitored by TLC and after completion of reaction product was filtered and residue was washed with acetic acid (1000 ml). Acetic acid was distilled under vacuum (550 mm of Hg) below 80° C. and water (8000 ml) was added, cooled to 25-30° C. and stirred for 30 min. The slurry was filtered and washed with water (1000 ml). Crude product was dried under heating at 70-80° C. for 2 hours, then was taken in 5% ethyl acetate/n-hexane (100:2000 ml) solution and stirred for 1-1.5 h at ambient temperature. The suspension was filtered and washed with 5% ethyl acetate/n-hexane mixture (25:475 ml). The product obtained was dried under vacuum at below 80° C. for 10-12 h to give 4-nitro-1H-indazole as a brown solid (150 g, 70%): mp: 200-203° C.; 1H NMR (200 MHz, CDCl3) δ 13.4 (br, 1H), 8.6 (s, 1H), 8.2-7.95 (dd, 2H), 7.4 (m, 1H). ESMS m/z 164 (M+1). Purity: 95% (HPLC)

1. additionAfter the addition
2. customthe reaction temp
3. temperaturewas increased to 25-30° C.
4. customReaction progress
5. customafter completion of reaction product
6. filtrationwas filtered
7. washresidue was washed with acetic acid (1000 ml)
8. distillationAcetic acid was distilled under vacuum (550 mm of Hg) below 80° C. and water (8000 ml)
9. additionwas added
10. temperaturecooled to 25-30° C.
11. stirringstirred for 30 min
12. filtrationThe slurry was filtered
13. washwashed with water (1000 ml)
14. customCrude product was dried
15. temperatureunder heating at 70-80° C. for 2 hours
16. stirringstirred for 1-1.5 h at ambient temperature
17. filtrationThe suspension was filtered
18. washwashed with 5% ethyl acetate/n-hexane mixture (25:475 ml)
19. customThe product obtained
20. customwas dried under vacuum at below 80° C. for 10-12 h

ORD record

ord-860f21a9b3074f919db3364e92ece4a0

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987280B2