Dimethylformamide → Methyl 1-methyl-1H-indazole-4-carboxylate

HRID 1662060Notes

Reaction equation

HRID 1662060 reaction equation
[H-].[Na+].[CH3:3][N:4]([CH:6]=O)[CH3:5].[NH:8]1[C:16]2[CH:15]=[CH:14][CH:13]=[C:12]([C:17]([O:19][CH3:20])=[O:18])[C:11]=2[CH:10]=[N:9]1.CI>O>[CH3:5][N:4]1[C:6]2[CH:15]=[CH:14][CH:13]=[C:12]([C:17]([O:19][CH3:20])=[O:18])[C:11]=2[CH:16]=[N:8]1.[CH3:3][N:9]1[CH:10]=[C:11]2[C:16]([CH:15]=[CH:14][CH:13]=[C:12]2[C:17]([O:19][CH3:20])=[O:18])=[N:8]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 6623327methyl 1H-indazole-4-carboxylate

Product 2

HCID 37818679Methyl 1-methyl-1H-indazole-4-carboxylateHCID 37818684Methyl 2-methyl-2H-indazole-4-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of sodium hydride (522 mg) and DMF (30 ml) was added methyl 1H-indazole-4-carboxylate (2.0 g) under ice-cooling, followed by stirring for 20 minutes. To the reaction mixture was added methyl iodide (1.41 ml), followed by stirring under ice-cooling for 30 minutes, and further at room temperature for 1 hour. The reaction mixture was ice-cooled, and water (100 ml) was added thereto, followed by stirring for 15 minutes. The insolubles were removed by filtration and the filtrate was extracted with ethyl acetate (80 ml). The organic layer was washed with a saturated sodium bicarbonate solution and saturated brine in this order and dried over anhydrous magnesium sulfate. The solvent was then removed by evaporation under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1→1:1) to obtain methyl 1-methyl-1H-indazole-4-carboxylate (900 mg) as a pale yellow solid and methyl 2-methyl-2H-indazole-4-carboxylate (600 mg) as a pale red oil.

Workup

  1. temperaturecooling
  2. stirringby stirring under ice-
  3. temperaturecooling for 30 minutes
  4. waitfurther at room temperature for 1 hour
  5. temperaturecooled
  6. stirringby stirring for 15 minutes
  7. customThe insolubles were removed by filtration
  8. extractionthe filtrate was extracted with ethyl acetate (80 ml)
  9. washThe organic layer was washed with a saturated sodium bicarbonate solution and saturated brine in this order
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customThe solvent was then removed by evaporation under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1→1:1)

Sources & evidence

ORD record
ord-e18190eb4cae476dba9a9353920d7e64
Source dataset
uspto-grants-2011_10
Patent number
US08030489B2

Reaction notes

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