Acetic Anhydride → 1-Acetyl-6-(acetoxymethyl)indazole

HRID 1634070Notes

Reaction equation

HRID 1634070 reaction equation
[C:1]([O:4][CH2:5][C:6]1[CH:7]=[C:8]([C:13]([CH3:16])=[CH:14][CH:15]=1)[NH:9][C:10](=[O:12])[CH3:11])(=[O:3])[CH3:2].C([O-])(=O)C.[K+].C(OC(=O)C)(=O)C.C(O[N:35]=O)CC(C)C.C1OCCOCCOCCOCCOCCOC1>C(Cl)(Cl)Cl.C(Cl)Cl>[C:10]([N:9]1[C:8]2[C:13](=[CH:14][CH:15]=[C:6]([CH2:5][O:4][C:1](=[O:3])[CH3:2])[CH:7]=2)[CH:16]=[N:35]1)(=[O:12])[CH3:11]

Participants

8

Reactant 5

HCID 7918Acetic AnhydrideHCID 8053Isoamyl NitriteHCID 2855718-Crown-6HCID 517044Potassium AcetateHCID 186772603-(acetoxymethyl)-6-methyl-N-(acetyl)aniline

Product 1

HCID 186161831-Acetyl-6-(acetoxymethyl)indazoleYield 95.8%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3-(acetoxymethyl)-6-methyl-N-(acetyl)aniline (10.0 g, 45 mmol) (3) and potassium acetate (8.6 g, 88 mmol) in chloroform (300 mL), was added acetic anhydride (8.3 mL, 88 mmol), isoamylnitrite (35 mL, 300 mmol) and 18-crown-6 (1.5 g, 0.6 mmol) at room temperature. The reaction mixture was heated at reflux for 28 hours. The reaction mixture was diluted with methylene chloride (600 mL) and washed with saturated NaHCO3 aqueous solution (300 mL), water (300 mL) and brine (50 mL). After drying (Na2SO4), the organic solvent was removed under vacuum to give a yellow oil which was purified by a flash chromatography on silica gel (85:15 hexane-ethyl acetate) to yield the title compound (4) (10.01 g, 95%). TLC Rf 0.47 (70:30 of hexane-ethyl acetate); MS (electrospray) 233 (M+1); 1H N MR (CDCl3) δ2.10 (s, 3H), 2.78 (s, 3H), 5.27 (s, 2H), 7.36 (d, 1H, J=8.0 Hz), 7.73 (d, 1H, J=8.0 Hz), 8.12 (s, 1H), 8.47 (s, 1H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 28 hours
  3. washwashed with saturated NaHCO3 aqueous solution (300 mL), water (300 mL) and brine (50 mL)
  4. dry with materialAfter drying (Na2SO4)
  5. customthe organic solvent was removed under vacuum
  6. customto give a yellow oil which
  7. customwas purified by a flash chromatography on silica gel (85:15 hexane-ethyl acetate)

Sources & evidence

ORD record
ord-d7eba3139379496bad00498156ea725c
Source dataset
uspto-grants-2003_01
Patent number
US06506754B1

Reaction notes

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