Acetic Anhydride → Methyl 6-chloro-1H-indazole-4-carboxylate

HRID 1501698Notes

Reaction equation

HRID 1501698 reaction equation
[NH2:1][C:2]1[C:3]([CH3:13])=[C:4]([CH:9]=[C:10]([Cl:12])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].C([O-])(=O)C.[K+].C(OC(=O)C)(=O)C.[N:26](OC(C)(C)C)=O.C1OCCOCCOCCOCCOCCOC1>C(Cl)(Cl)Cl>[Cl:12][C:10]1[CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[C:3]2[CH:13]=[N:26][NH:1][C:2]=2[CH:11]=1

Participants

7

Reactant 5

HCID 7918Acetic AnhydrideHCID 10906Tert-Butyl nitriteHCID 2855718-Crown-6HCID 517044Potassium AcetateHCID 68295455Methyl 3-amino-5-chloro-2-methylbenzoate

Product 1

HCID 24728139Methyl 6-chloro-1H-indazole-4-carboxylateYield 90%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

To a stirred solution of methyl 3-amino-5-chloro-2-methylbenzoate (1 equiv.) in chloroform (13 mL per 1 mmol), potassium acetate (1.05 equiv.) and acetic anhydride (2 equiv.) were added and reaction mixture stirred at room temperature for 12 h. After this time, tert-butyl nitrite (4 equiv.) and 18-crown-6 (0.35 equiv.) were added and the reaction stirred again at 65° C. for 3 h. On completion, the reaction mixture 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 (yield 90-95%).

Workup

  1. customreaction mixture
  2. stirringthe reaction stirred again at 65° C. for 3 h
  3. temperatureOn completion, the reaction mixture 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-70b183361bf14815b50be1adb63e74af
Source dataset
uspto-grants-2015_12
Patent number
US09206157B2

Reaction notes

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