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

HRID 1263437Notes

Reaction equation

HRID 1263437 reaction equation
[OH:1][CH2:2][C:3]1[CH:4]=[C:5]([C:10]([CH3:13])=[CH:11][CH:12]=1)[NH:6][C:7]([CH3:9])=[O:8].[C:14]([O-:17])(=O)[CH3:15].[K+].C(OC(=O)C)(=O)C.C(O[N:32]=O)CC(C)C.C1OCCOCCOCCOCCOCCOC1>C(Cl)(Cl)Cl.C(Cl)Cl>[C:7]([N:6]1[C:5]2[C:10](=[CH:11][CH:12]=[C:3]([CH2:2][O:1][C:14](=[O:17])[CH3:15])[CH:4]=2)[CH:13]=[N:32]1)(=[O:8])[CH3:9]

Participants

8

Reactant 5

HCID 7918Acetic AnhydrideHCID 8053Isoamyl NitriteHCID 2855718-Crown-6HCID 517044Potassium AcetateHCID 14543056N-[5-(Hydroxymethyl)-2-methylphenyl]acetamide

Product 1

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

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3-(hydroxymethyl)-6-methyl-N-(methylcarbonyl)aniline (10.0 g, 45 mmol) (97) 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 its reflux temperature 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 (98) (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 at its
  2. temperaturereflux temperature 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-64c14c5968a14aba9be7f876864dfaaa
Source dataset
uspto-grants-2003_04
Patent number
US06541467B1

Reaction notes

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