Hydrochloric Acid → 5,6-Dichloro-1H-indazole-3-acetic acid

Temperature

65 °C

To a stirred mixture of 4,5-dichloro-2-nitrobenzaldehyde (1.1 g, 5.00 mmol) and malonic acid (676 mg, 6.5 mmol) in formic acid (3 mL) at 40° C., ammonium formate (768 mg, 12.5 mmol) was added. The resulting mixture was stirred at 65° C. for 1 h and then at 95° C. for 4 h. To this mixture, conc. HCl (2.5 mL) was added and then stirred at 95° C. for 1 h. The mixture was allowed to cool to room temperature, quenched with water (5 mL) and extracted with isobutyl ketone. The aqueous layer was adjusted the pH to 4 with KOH (50%) and filtered to afford the crude solid (500 mg). The solid was dissolved in a mixture of NaOH aqueous solution (8 mL, 5%) and N2H4.H2O (90 mg, 1.79 mmol) and heated to 85° C. To this mixture, Raney-Ni was added and the resulting mixture was stirred at 85° C. for 30 min. The mixture was allowed to cool to room temperature and filtered. The aqueous layer was acidified with aqueous HCl (6 M) to adjust the pH to 2. The precipitate was collected by filtration and dried in vacuo to afford the desired product (250 mg, yield 22%, 2 steps).

1. waitat 95° C. for 4 h
2. stirringstirred at 95° C. for 1 h
3. temperatureto cool to room temperature
4. customquenched with water (5 mL)
5. extractionextracted with isobutyl ketone
6. filtrationfiltered
7. customto afford the crude solid (500 mg)
8. temperatureheated to 85° C
9. stirringthe resulting mixture was stirred at 85° C. for 30 min
10. temperatureto cool to room temperature
11. filtrationfiltered
12. filtrationThe precipitate was collected by filtration
13. customdried in vacuo

ORD record

ord-fed32cb1e45d429a8d11233bbbe504b1

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09227978B2