Methyl iodide → methyl 1H-indazole-6-carboxylate

HRID 711057Notes

Reaction equation

HRID 711057 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([OH:12])=[O:11])[CH:8]=2)[CH:3]=[N:2]1.[C:13](=O)([O-])[O-].[Na+].[Na+].IC.C(=O)(O)[O-].[Na+]>CN(C)C=O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:10]([O:12][CH3:13])=[O:11])[CH:8]=2)[CH:3]=[N:2]1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 162279381H-indazole-6-carboxylic acid

Product 1

HCID 286535methyl 1H-indazole-6-carboxylateYield 90.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1H-indazole-6-carboxylic acid (3.00 g, 18.5 mmol) in N,N-dimethylformamide (46 mL) was added sodium carbonate (2.06 g, 19.4 mmol), followed by iodomethane (2.75 g, 1.21 mL, 19.4 mmol) dropwise. The mixture was stirred at room temperature overnight. The mixture was poured into half saturated sodium bicarbonate and extracted with ethyl acetate three times. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a brown oil. This residue was purified by flash column chromatography (12-100% ethyl acetate/heptanes) to afford methyl 1H-indazole-6-carboxylate as a yellow solid (2.95 g, 90%). 1H NMR (400 MHz, CDCl3, δ): 10.40 (br. s., 1H), 8.26 (s, 1H), 8.13 (s, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.79 (d, J=8.4 Hz, 1H), 3.96 (s, 3H).

Workup

  1. extractionextracted with ethyl acetate three times
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto afford a brown oil
  7. customThis residue was purified by flash column chromatography (12-100% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-d68c826b457b467e988894cae8d530a9
Source dataset
uspto-grants-2015_11
Patent number
US09181252B2

Reaction notes

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