Methyl iodide → HCID 178469303, compound

HRID 1880357Notes

Reaction equation

HRID 1880357 reaction equation
[CH2:1]([C:3]1[C:11]2[C:6](=[C:7]([OH:17])[CH:8]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:10]=2)[NH:5][N:4]=1)[CH3:2].[H-].[Na+].I[CH3:21]>CN(C=O)C.CCOC(C)=O>[CH2:1]([C:3]1[C:11]2[C:6](=[C:7]([O:17][CH3:21])[CH:8]=[C:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:10]=2)[NH:5][N:4]=1)[CH3:2]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178469297HCID 178469297, compound

Product 1

HCID 178469303HCID 178469303, compoundYield 100.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of ethyl 3-ethyl-7-hydroxy-1H-indazole-5-carboxylate (2.47 g, 10.5 mmo) in DMF (40 mL) was cooled to 0° C. To this mixture was added 60% NaH (0.42 g, 10.5 mmol) and stirred for 1 hour. To this was added a 0° C. solution of iodomethane (1.50 g, 0.66 mL, 10.5 mmol) in DMF (10 mL). The mixture was kept at 0° C. for several hours before stirring at room temperature overnight. The mixture was diluted with EtOAc, washed with a mixture of saturated aqueous NaHCO3 and saturated aqueous NaCl followed by saturated aqueous NaCl. The organic extract was dried over Na2SO4, filtered and concentrated. Purify by CombiFlash (80 g column, 0-30% EtOAc/hexanes gradient) to provide ethyl 3-ethyl-7-methoxy-1H-indazole-5-carboxylate (2.62 g, 40%).

Workup

  1. waitThe mixture was kept at 0° C. for several hours
  2. stirringbefore stirring at room temperature overnight
  3. washwashed with a mixture of saturated aqueous NaHCO3 and saturated aqueous NaCl
  4. extractionThe organic extract
  5. dry with materialwas dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurify by CombiFlash (80 g column, 0-30% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-6d6bd3fa4588446298f774af083ae1d6
Source dataset
uspto-grants-2012_11
Patent number
US08318762B2

Reaction notes

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