Tert-Butyl nitrite → Methyl 1-acetylindazole-3-carboxylate

HRID 1372735Notes

Reaction equation

HRID 1372735 reaction equation
[C:1]([NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH2:11][C:12]([O:14][CH3:15])=[O:13])(=[O:3])[CH3:2].[N:16](OC(C)(C)C)=O>C(O)(=O)C.O.C(OC(=O)C)(=O)C>[C:1]([N:4]1[C:5]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:11]([C:12]([O:14][CH3:15])=[O:13])=[N:16]1)(=[O:3])[CH3:2]

Participants

6

Reactant 2

HCID 10906Tert-Butyl nitriteHCID 10954745Methyl 2-(2-acetamidophenyl)acetate

Product 1

HCID 3681967Methyl 1-acetylindazole-3-carboxylateYield 85.2%

Reagents, catalysts & solvents 3

HCID 7918Acetic AnhydrideCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

Methyl (2-acetamidophenyl)acetate (24.3 g, 0.12 mol) and acetic anhydride (24.3 ml, 0.26 mmol) were dissolved in acetic acid (60 ml). To the resulting solution, tert-butyl nitrite (90% purity, 18.6 ml, 0.14 mol) was added dropwise over 20 minutes under stirring at 90° C. After completion of the dropwise addition, the reaction mixture was stirred at 90° C. for further 1 hour. The reaction mixture was cooled to room temperature and then, poured in water (500 ml), followed by stirring for 1 hour. The crystals thus precipitated were collected by filtration under reduced pressure and dissolved in chloroform. The chloroform solution was washed with a saturated aqueous solution of sodium bicarbonate and saturated brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove the solvent, whereby methyl 1-acetylindazole-3-carboxylate (22.3 g, 85%) was obtained as a yellow solid.

Workup

  1. additionAfter completion of the dropwise addition
  2. stirringthe reaction mixture was stirred at 90° C. for further 1 hour
  3. temperatureThe reaction mixture was cooled to room temperature
  4. stirringby stirring for 1 hour
  5. customThe crystals thus precipitated
  6. filtrationwere collected by filtration under reduced pressure
  7. dissolutiondissolved in chloroform
  8. washThe chloroform solution was washed with a saturated aqueous solution of sodium bicarbonate and saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. distillationdistilled under reduced pressure
  11. customto remove the solvent

Sources & evidence

ORD record
ord-28e170d0f4f6477c9d6a720f108ac4db
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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