Acetic Anhydride → methyl 6-(trifluoromethyl)-1H-indazole-4-carboxylate

HRID 1909332Notes

Reaction equation

HRID 1909332 reaction equation
[NH2:1][C:2]1[C:3]([CH3:16])=[C:4]([CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].C([O-])(=O)C.[K+].C(OC(=O)C)(=O)C.[N:29](OC(C)(C)C)=O.C1OCCOCCOCCOCCOCCOC1>C(Cl)(Cl)Cl>[F:15][C:12]([F:13])([F:14])[C:10]1[CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[C:3]2[CH:16]=[N:29][NH:1][C:2]=2[CH:11]=1

Participants

7

Reactant 5

HCID 7918Acetic AnhydrideHCID 10906Tert-Butyl nitriteHCID 2855718-Crown-6HCID 517044Potassium AcetateHCID 68295733Methyl 3-amino-2-methyl-5-(trifluoromethyl)benzoate

Product 1

HCID 69441140methyl 6-(trifluoromethyl)-1H-indazole-4-carboxylateYield 90%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

To a stirred solution of methyl 3-amino-2-methyl-5-(trifluoromethyl)benzoate (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 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 title the compound (yield 90-95%).

Workup

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

Sources & evidence

ORD record
ord-f90f2edad0174f2d90509b454bec7318
Source dataset
uspto-grants-2013_12
Patent number
US08598167B1

Reaction notes

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