Acetic Anhydride → 1-(5-Nitro-1H-indazol-1-yl)ethan-1-one

HRID 1013826Notes

Reaction equation

HRID 1013826 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[CH:7]2)([O-:3])=[O:2].C(N(CC)CC)C.[C:20](OC(=O)C)(=[O:22])[CH3:21].CCOC(C)=O>C1COCC1>[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([C:20](=[O:22])[CH3:21])[N:8]=[CH:7]2)([O-:3])=[O:2]

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 215015-Nitroindazole

Product 1

HCID 232708801-(5-Nitro-1H-indazol-1-yl)ethan-1-oneYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Step 1) Dissolve commercially available 5-nitroindazole (100 g, 613 mmoles) in 2 L of THF and then add triethylamine (260 mL; 1.87 moles). Stir the solution at room temp until all the solid went into the solution, and then add acetic acid anhydride (94 g; 927 mmoles). After 2 h at room temperature, add 2 L of EtOAc and extract the mixture with 1 N HCl (2×800 mL). Wash the organic layer with aqueous sodium bicarbonate followed by saturated aqueous NaCl. Dry the organic layer with magnesium sulfate and concentrate to a thick slurry. Add t-Butyl methyl ether (300 mL) and filter the slurry. Collect the solid, rinse with t-butyl methyl ether, and dry under vacuum to afford 113 g (90%) of 1-(5-nitro-indazol-1-yl)-ethanone a pale yellow solid. 1H NMR (500 MHz, CDCl3) δ 8.70 (d, 1H, J=2.0 Hz), 8.58 (d, 1H, J=9.5 Hz), 8.44 (dd, 1H J=7.0, 2.0 Hz), 8.31 (s, 1H), 2.84 (s, 1H).

Workup

  1. extractionextract the mixture with 1 N HCl (2×800 mL)
  2. washWash the organic layer with aqueous sodium bicarbonate
  3. dry with materialDry the organic layer with magnesium sulfate
  4. concentrationconcentrate to a thick slurry
  5. filtrationAdd t-Butyl methyl ether (300 mL) and filter the slurry
  6. customCollect the solid
  7. washrinse with t-butyl methyl ether
  8. customdry under vacuum

Sources & evidence

ORD record
ord-697b58bbbea44315b296205f50e5367f
Source dataset
uspto-grants-2011_07
Patent number
US07981918B2

Reaction notes

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