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

HRID 1854145Notes

Reaction equation

HRID 1854145 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-b52f9128b61f484893cfb263a7dce9f6
Source dataset
uspto-grants-2015_02
Patent number
US08962620B2

Reaction notes

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