Indazole-3-carboxylic acid → methyl 1H-indazole-3-carboxylate

HRID 2206468Notes

Reaction equation

HRID 2206468 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([OH:12])=[O:11])=[N:2]1.[C:13](=O)(O)[O-].[Na+]>CO.S(Cl)(Cl)=O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([O:12][CH3:13])=[O:11])=[N:2]1

Participants

5

Reactant 2

HCID 78250Indazole-3-carboxylic acidHCID 516892Sodium Bicarbonate

Product 1

HCID 657476methyl 1H-indazole-3-carboxylateYield 94%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 24386Thionyl ChlorideSolvent

Procedure

To a solution of 1H-indazole-3-carboxylic acid (5.0 g, 30.8 mmol) in methanol (50 mL), thionyl chloride (15 mL) was added dropwise at 0° C. After the addition, the mixture was heated to reflux and maintained at the temperature for 1.5 hours. Then the reaction mixture was concentrated to give a residue. To the residue was added saturated sodium bicarbonate (50 mL), and then extracted with ethyl acetate (50 mL×3). The organic phase was combined and dried over anhydrous sodium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure to give methyl 1H-indazole-3-carboxylate as a white solid (5.1 g, 94%). 1H NMR (300 MHz, d6-DMSO): δ 13.91 (s, 1H), 8.06 (d, J=8.2 Hz, 1H), 7.65 (d, J=8.4 Hz, 1H), 7.44 (ddd, J=8.3 Hz, J=6.9 Hz, J=1.1 Hz, 1H), 7.30 (ddd, J=7.9 Hz, J=6.9 Hz, J=0.9 Hz, 1H), 3.92 (s, 3H).

Workup

  1. additionAfter the addition
  2. temperaturethe mixture was heated
  3. temperatureto reflux
  4. temperaturemaintained at the temperature for 1.5 hours
  5. concentrationThen the reaction mixture was concentrated
  6. customto give a residue
  7. extractionextracted with ethyl acetate (50 mL×3)
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationThe mixture was filtered
  10. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-28689c9b64954f5e8467fb72e8cf28bd
Source dataset
uspto-grants-2016_06
Patent number
US09371331B2

Reaction notes

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