Acetic Anhydride → Methyl 1-acetyl-1H-indazole-5-carboxylate

HRID 22656

Reaction equation

HRID 22656 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[NH2:12])[C:5]([O:7][CH3:8])=[O:6].[C:13]([O-:16])(=O)[CH3:14].[K+].C(OC(=O)C)(=O)C.C1OCCOCCOCCOCCOCCOC1.CCCCCO[N:49]=O>C(Cl)(Cl)Cl>[C:13]([N:12]1[C:11]2[C:2](=[CH:3][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:9][CH:10]=2)[CH:1]=[N:49]1)(=[O:16])[CH3:14]

Participants

7

Reactant 5

HCID 7918Acetic AnhydrideHCID 10026Pentyl nitriteHCID 2855718-Crown-6HCID 517044Potassium AcetateHCID 2736799Methyl 4-amino-3-methylbenzoate

Product 1

HCID 22591332Methyl 1-acetyl-1H-indazole-5-carboxylateYield 47.4%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a stirred mixture of methyl 3-methyl-4-aminobenzoate (5.0 g, 30.0 mmol) and potassium acetate (2.94 g, 30.0 mmol) in chloroform (50 mL) is added acetic anhydride (5.66 mL, 60.0 mmol). The mixture is stirred for 30 min at rt, followed by the addition of 18-crown-6 (1.58 g, 6.0 mmol) and n-amyl nitrite (7.78 g, 66.0 mmol). The mixture is heated to reflux for 16 h, followed by cooling to rt. The mixture is washed sequentially with aqueous sodium bicarbonate solution (2×), water and brine. The organic layer is dried over MgSO4, filtered and concentrated in vacuo. The crude product is purified by flash chromatography on silica gel. Elution with hexanes-EtOAc (80:20) gives 3.1 g (47%) of methyl 1-acetyl-1H-indazole-5-carboxylate as a yellow solid: 1H NMR (400 MHz, CDCl3) δ 8.52-8.50, 8.3, 8.2, 4.0, 2.8.

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux for 16 h
  3. temperatureby cooling to rt
  4. washThe mixture is washed sequentially with aqueous sodium bicarbonate solution (2×), water and brine
  5. dry with materialThe organic layer is dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product is purified by flash chromatography on silica gel
  9. washElution with hexanes-EtOAc (80:20)

Sources & evidence

ORD record
ord-6062662749034ec397236ef61309513e
Source dataset
uspto-grants-2005_02
Patent number
US06849620B2

Linked notes

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