Acetic Anhydride → 1H-indazol-4-ol

Acetic anhydride (16.4 ml, 174 mmol), tetrabutylammonium bromide (933 mg, 2.90 mmol), potassium acetate (11.4 g, 116 mmol) and isoamyl nitrite (11.7 ml, 86.9 mmol) were added to a solution of 3-(acetylamino)-2-methylphenyl acetate (12.0 g, 57.9 mmol) in ethyl acetate (120 ml) at room temperature, and the resulting mixture was refluxed for 7 hours. The reaction solution was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent, and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=3/1). Subsequently, the residue purified was dissolved in methanol (50 ml) and a 2N-aqueous sodium hydroxide solution (47.9 ml) was added thereto at room temperature and stirred for 1 hour. The methanol was distilled off under reduced pressure, and the resulting aqueous solution was adjusted to pH 4 to 5 by dropwise addition of hydrochloric acid and then extracted with acetic acid. The organic layer was dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent, and the resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=2/1) to obtain 1H-indazol-4-ol (3.62 g, 47%).

1. temperaturethe resulting mixture was refluxed for 7 hours
2. extractionextracted with ethyl acetate
3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
4. distillationdistilled under reduced pressure
5. customto remove the solvent
6. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=3/1)
7. customSubsequently, the residue purified
8. dissolutionwas dissolved in methanol (50 ml)
9. additiona 2N-aqueous sodium hydroxide solution (47.9 ml) was added
10. distillationThe methanol was distilled off under reduced pressure
11. additionthe resulting aqueous solution was adjusted to pH 4 to 5 by dropwise addition of hydrochloric acid
12. extractionextracted with acetic acid
13. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
14. distillationdistilled under reduced pressure
15. customto remove the solvent
16. customthe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=2/1)

ORD record

ord-611a0670e3e94a5899a076a360d28444

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07199147B2