Sodium Carbonate → 6-hydroxy-1H-indazole

Temperature

0 °C

Indazol-6-amine (24.33 g; manufactured by Tokyo Chemical Industry, Co., Ltd.) was dissolved in water (100 mL) and 48% by weight of tetrafluoroboric acid solution (242 mL; manufactured by Sigma-Aldrich Co.). After cooling to 0° C., an aqueous solution of sodium nitrite [20 mL (sodium nitrite (13.87 g; manufactured by Kanto Chemical Co., Inc.) was dissolved in water (20 mL) to give the solution] was added dropwise thereto for 10 minutes, followed by stirring at 0° C. for 30 minutes. The precipitate from the reaction solution was filtered and washed with chloroform. Thus-obtained precipitate was dissolved in acetic acid (250 mL) and stirred for 10 minutes at 50° C., 10 minutes at 110° C., and 10 minutes at 130° C. The reaction solution was cooled and added with a saturated aqueous solution of sodium carbonate, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and then dried. Thereafter, the solvent was evaporated under reduced pressure. Thus-obtained residue was dissolved in ethanol (240 mL), added with an aqueous solution of 2 mol/L-sodium hydroxide (365 mL), followed by stirring at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure, and 2 mol/L-hydrochloric acid (200 mL), water and a saturated aqueous solution of ammonium chloride were added to the residue to obtain pH 7 approximately, and the extraction was carried out with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. To the residue, chloroform was added, and then the insoluble matters were filtered, washed with chloroform to obtain the target compound as a crude product (13.5401 g).

1. customto give the solution]
2. additionwas added dropwise
3. filtrationThe precipitate from the reaction solution was filtered
4. washwashed with chloroform
5. customThus-obtained precipitate
6. stirringstirred for 10 minutes at 50° C., 10 minutes at 110° C.
7. custom10 minutes
8. customat 130° C
9. temperatureThe reaction solution was cooled
10. extractionfollowed by extraction with ethyl acetate
11. washThe organic layer was washed with brine
12. dry with materialdried over anhydrous magnesium sulfate
13. customdried
14. customThereafter, the solvent was evaporated under reduced pressure
15. dissolutionThus-obtained residue was dissolved in ethanol (240 mL)
16. additionadded with an aqueous solution of 2 mol/L-sodium hydroxide (365 mL)
17. stirringby stirring at room temperature for 1 hour
18. concentrationThe reaction solution was concentrated under reduced pressure, and 2 mol/L-hydrochloric acid (200 mL), water
19. additiona saturated aqueous solution of ammonium chloride were added to the residue
20. customto obtain pH 7 approximately
21. extractionthe extraction
22. washThe organic layer was washed with brine
23. dry with materialdried over anhydrous magnesium sulfate
24. customthe solvent was evaporated under reduced pressure
25. additionTo the residue, chloroform was added
26. filtrationthe insoluble matters were filtered
27. washwashed with chloroform

ORD record

ord-c580faf72b7e4ca68c6dfe35d01afea6

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08304443B2