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

HRID 1526953Notes

Reaction equation

HRID 1526953 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-51543e77cc624ea7a2b7bc8bf32387ba
Source dataset
uspto-grants-2015_07
Patent number
US09085583B2

Reaction notes

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