Methyl 3-amino-4-methylbenzoate → methyl 1H-indazole-6-carboxylate

HRID 1391512Notes

Reaction equation

HRID 1391512 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH3:12])[C:5]([O:7][CH3:8])=[O:6].[N:13]([O-])=O.[Na+]>C(O)(=O)C.O>[CH3:8][O:7][C:5]([C:4]1[CH:3]=[C:2]2[C:11]([CH:12]=[N:13][NH:1]2)=[CH:10][CH:9]=1)=[O:6]

Participants

5

Reactant 2

HCID 337778Methyl 3-amino-4-methylbenzoateHCID 23668193Sodium Nitrite

Product 1

HCID 286535methyl 1H-indazole-6-carboxylateYield 73.8%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

To a stirred solution of methyl 3-amino-4-methylbenzoate (4.98 g, 30 mmol) in acetic acid (50 mL) was added sodium nitrite (2.29 g, 33.0 mmol) in water (5 mL) dropwise at 0° C. After 5 min a solid precipitated. The cooling bath was removed and the reaction mixture was brought to room temperature. More acetic acid (50 mL) was added to dissolve the precipitate; this was stirred for 2 h, and a clear dark solution appeared. After 4 h, acetic acid was evaporated and the residue was added to a saturated aqueous sodium bicarbonate solution; this was extracted with ethyl acetate (3×60 mL). The combined extracts were washed with brine (10 mL), dried (MgSO4) and evaporated. The residue solidified upon standing at room temperature to give an amorphous solid (3.9 g, 73%): MS (ES) m/z 177 (M+); 1H NMR (CDCl3): 10.05 (1H, br s), 8.29 (1H, s), 8.16 (1H, s), 7.86 (1H, d, J=8.0 Hz), 7.81 (1H, d, J=8.0 Hz), 3.97 (3H, s).

Workup

  1. customAfter 5 min a solid precipitated
  2. customThe cooling bath was removed
  3. customwas brought to room temperature
  4. additionMore acetic acid (50 mL) was added
  5. dissolutionto dissolve the precipitate
  6. waitAfter 4 h
  7. customacetic acid was evaporated
  8. additionthe residue was added to a saturated aqueous sodium bicarbonate solution
  9. extractionthis was extracted with ethyl acetate (3×60 mL)
  10. washThe combined extracts were washed with brine (10 mL)
  11. dry with materialdried (MgSO4)
  12. customevaporated
  13. customupon standing at room temperature

Sources & evidence

ORD record
ord-f37db6be8cf04c99b8d4cebe91d8e7c4
Source dataset
uspto-grants-2008_03
Patent number
US07338972B1

Reaction notes

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