Acetic Anhydride → 1H-Indazole-4-carboxylic acid, 1-acetyl-6-bromo-, methyl ester

HRID 1501656Notes

Reaction equation

HRID 1501656 reaction equation
[NH2:1][C:2]1[C:3]([CH3:13])=[C:4]([CH:9]=[C:10]([Br:12])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:14]([O-:17])(=O)[CH3:15].[K+].C(OC(=O)C)(=O)C.[N:26](OC(C)(C)C)=O.C1OCCOCCOCCOCCOCCOC1>C(Cl)(Cl)Cl>[C:14]([N:1]1[C:2]2[CH:11]=[C:10]([Br:12])[CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[C:3]=2[CH:13]=[N:26]1)(=[O:17])[CH3:15]

Participants

7

Reactant 5

HCID 7918Acetic AnhydrideHCID 10906Tert-Butyl nitriteHCID 2855718-Crown-6HCID 517044Potassium AcetateHCID 24729181Methyl 3-Amino-5-bromo-2-methylbenzoate

Product 1

HCID 682954331H-Indazole-4-carboxylic acid, 1-acetyl-6-bromo-, methyl esterYield 98.5%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

To a stirred solution of methyl 3-amino-5-bromo-2-methylbenzoate (15 g, 61.5 mmol) in chloroform (150 mL), was added potassium acetate (6.32 g, 64.4 mmol) and acetic anhydride (12.6 g, 122.9 mmol) and reaction mixture was stirred at room temperature for 12 h. After this time, tert-butyl nitrite (25.3 g, 246.1 mmol) and 18-crown-6 (5.7 g, 21.5 mmol) were added and reaction stirred again at 65° C. for 3 h. On completion, the reaction mass was cooled to room temperature, diluted with chloroform (500 mL) and washed with sat. sodium bicarbonate solution. The organic layer was dried over sodium sulfate and concentrated to afford the title compound (18 g, 98.3%).

Workup

  1. customreaction
  2. stirringstirred again at 65° C. for 3 h
  3. temperatureOn completion, the reaction mass was cooled to room temperature
  4. washwashed with sat. sodium bicarbonate solution
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-da441b6693144fb99dd2082cf563832e
Source dataset
uspto-grants-2015_12
Patent number
US09206157B2

Reaction notes

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