Sulfuric Acid → Indazole-3-carboxylic acid

Temperature

0 °C

A solution of concentrated sulfuric acid (19.1 g, 0.19 mol) in water (200 ml) prepared in a 2 litre beaker was cooled to 0° C. Isatin (14.7 g, 0.1 mol) was added to a solution of sodium hydroxide (4.1 g, 0.105 mol) in water(65 ml) at 50° C. and the dark red solution cooled to 0° C. A solution of sodium nitrite (6.9 g, 0.1 mol) in water (235 ml) at 0° C. was added and the mixture added to the rapidly stirred solution of sulfuric acid during 5 minutes. The temperature was not allowed to rise above 4° C. (controlled by the addition of ice). The yellow brown foamy mixture was stirred for a further 15 minutes before being treated with a solution of stannous chloride hydrate (54 g, 0.24 mol) in concentrated hydrochloric acid (85 ml) at 0° C. The mixture was stirred for one hour and the crude product filtered. The material was recrystallized as follows: about half of the solid was placed in a 1 litre flask and ~500 ml of water was added. The solution was heated on a hot-plate until boiling and was then filtered hot to give a dark yellow-brown precipitate and an orange-yellow solution. The solution was left to cool overnight. The recrystallizing solution was filtered to give a yellow solid and a pale yellow filtrate. The solid was put in the oven to dry. The process was repeated with the other half of the crude product and the two mother liquors were pooled together as were the solid products. The dark yellow-brown substance filtered off during recrystallization was boiled with 150 ml of water, filtered and the resulting solution was left to recrystallize. It was then treated as above. The pooled mother liquors were concentrated to 1/3 volume and the solution allowed to crystallize. The solid thus obtained was added to the rest. On drying, 7.27 g solid yellow powder product was obtained, with an m.p. 263-264° C.

1. temperaturethe dark red solution cooled to 0° C
2. customto rise above 4° C.
3. additioncontrolled by the addition of ice)
4. stirringThe mixture was stirred for one hour
5. filtrationthe crude product filtered
6. customThe material was recrystallized
7. customabout half of the solid was placed in a 1 litre flask
8. addition~500 ml of water was added
9. temperatureThe solution was heated on a hot-plate
10. filtrationwas then filtered hot
11. customto give a dark yellow-brown precipitate
12. waitThe solution was left
13. temperatureto cool overnight
14. filtrationThe recrystallizing solution was filtered
15. customto give a yellow solid
16. customto dry
17. filtrationThe dark yellow-brown substance filtered off during recrystallization
18. filtrationfiltered
19. waitthe resulting solution was left
20. customto recrystallize
21. additionIt was then treated as above
22. concentrationThe pooled mother liquors were concentrated to 1/3 volume
23. customto crystallize
24. customThe solid thus obtained
25. additionwas added to the rest
26. customOn drying

ORD record

ord-6eda864c050240d989dc9a19fb1ba0ca

Source dataset

uspto-grants-1999_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05955470