Boron trifluoride etherate → 1H-indazole-6-carboxylic acid

To a solution of boron trifluoride etherate (18 ml) in chloroform (450 ml, Al2O3 treated) at -15° was added a solution of 3-amino-4-methylbenzoic acid (15.1 g) in tetrahydrofuran (150 ml) over 15 minutes and the resulting mixture was then stirred for an additional 5 minutes. To this mixture was added t-butyl nitrite (14 ml), and the reaction was warmed to 5° . After stirring for 1 hour, potassium acetate (49 g) and 18-crown-6 (2.65 g) were added. The reaction mixture was allowed to warm to room temperature and stirred for 72 hours. The reaction mixture was evaporated, and 3:7 acetone:ethyl acetate (500 ml) and 1N hydrochloric acid (150 ml) were added. After stirring for 2 hours, brine (150 ml) was added to the mixture and the mixture filtered. The aqueous filtrate was extracted with 3:7 acetone:ethyl acetate (2×100 ml). The combined organic extract was dried (MgSO4) and evaporated. The resulting residue was dissolved in hot acetic acid (250 ml) and 250 ml saturated ethereal HCl and 250 ml ether were added sequentially. After cooling to room temperature, the precipitate was filtered and treated with 3:7 acetone:ethyl acetate (500 ml) and brine (100 ml) for 1 hour. After the phases were separated, the aqueous layer was extracted with ethyl acetate (100 ml). The combined organic extracts were washed with brine, dried (MgSO4) and evaporated to afford 6-carboxyindazole as a brown solid (9.8 g, 57%), mp >250°.

1. temperaturethe reaction was warmed to 5°
2. stirringAfter stirring for 1 hour
3. stirringstirred for 72 hours
4. customThe reaction mixture was evaporated
5. addition3:7 acetone:ethyl acetate (500 ml) and 1N hydrochloric acid (150 ml) were added
6. stirringAfter stirring for 2 hours
7. additionbrine (150 ml) was added to the mixture
8. filtrationthe mixture filtered
9. extractionThe aqueous filtrate was extracted with 3:7 acetone
10. extractionThe combined organic extract
11. dry with materialwas dried (MgSO4)
12. customevaporated
13. dissolutionThe resulting residue was dissolved in hot acetic acid (250 ml)
14. addition250 ml saturated ethereal HCl and 250 ml ether were added sequentially
15. temperatureAfter cooling to room temperature
16. filtrationthe precipitate was filtered
17. additiontreated with 3:7 acetone
18. waitethyl acetate (500 ml) and brine (100 ml) for 1 hour
19. customAfter the phases were separated
20. extractionthe aqueous layer was extracted with ethyl acetate (100 ml)
21. washThe combined organic extracts were washed with brine
22. dry with materialdried (MgSO4)
23. customevaporated

ORD record

ord-8f64b2115e594e1b950b8515a887a33e

Source dataset

uspto-grants-1990_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04898863