Acetic Anhydride → ethyl 1-acetyl-7-(acetyloxy)-3-ethyl-1H-indazole-5-carboxylate

HRID 1880355Notes

Reaction equation

HRID 1880355 reaction equation
[CH2:1]([C:3]1[C:7]([CH:8]=[C:9]([CH2:15][C:16](=[O:18])C)[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][NH:5][N:4]=1)[CH3:2].[C:19]([O-:22])(=O)[CH3:20].[Na+].C([O-])(O)=O.[Na+].[C:29](OC(=O)C)(=[O:31])[CH3:30]>>[C:29]([N:5]1[C:6]2[C:7](=[CH:8][C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:15][C:16]=2[O:18][C:19](=[O:22])[CH3:20])[C:3]([CH2:1][CH3:2])=[N:4]1)(=[O:31])[CH3:30]

Participants

5

Reactant 4

HCID 7918Acetic AnhydrideHCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 178471161HCID 178471161, compound

Product 1

HCID 66920539ethyl 1-acetyl-7-(acetyloxy)-3-ethyl-1H-indazole-5-carboxylateYield 34%

Procedure

A solution of crude ethyl 2-[(3-ethyl-1H-pyrazol-4-yl)methylene]-4-oxopentanoate (4 g, 15.8 mmol) in acetic anhydride (10 mL), sodium acetate (2.6 g, 32 mmol) was added at room temperature and the mixture was heated at reflux for 4 h. The reaction mixture was cooled to room temperature, basified (pH ˜9) using aqueous NaHCO3 solution and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water (25 mL), saturated aqueous NaCl (25 mL), dried over anhydrous Na2SO4 and concentrated to obtain the crude product; which was purified by column chromatography (60-120 mesh silica gel) using 2-3% ethyl acetate in pet-ether as eluents to afford ethyl 1-acetyl-7-(acetyloxy)-3-ethyl-1H-indazole-5-carboxylate (1.7 g, 34%) as brown solid. 1H NMR (CDCl3) δ 8.44 (s, 1H), 8.24 (s, 1H), 4.58 (q, 2H), 3.2 (s, 3H), 2.9 (s, 3H), 2.58 (s, 3H), 1.6 (t, 3H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 4 h
  3. extractionextracted with ethyl acetate (2×50 mL)
  4. washThe combined organic layers were washed with water (25 mL), saturated aqueous NaCl (25 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customto obtain the crude product
  8. customwhich was purified by column chromatography (60-120 mesh silica gel)

Sources & evidence

ORD record
ord-bae37d94b7a14a639708306064d10138
Source dataset
uspto-grants-2012_11
Patent number
US08318762B2

Reaction notes

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