Sodium hydride → HCID 11673727, compound

HRID 1817504Notes

Reaction equation

HRID 1817504 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18]C)[CH:13]=2)=[O:11])=[N:2]1.[H-].[Na+].[H][H].Br[CH:25]=[C:26]([CH3:28])[CH3:27].[Cl-].[Li+]>CN(C=O)C.O.C(OCC)(=O)C>[OH:18][C:14]1[CH:13]=[C:12]([C:10]([C:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[N:1]([CH2:27][C:26]([CH3:28])=[CH2:25])[N:2]=2)=[O:11])[CH:17]=[CH:16][CH:15]=1

Participants

9

Reactant 5

HCID 24758Sodium hydrideHCID 985601-Bromo-2-methyl-1-propeneHCID 433294Lithium ChlorideHCID 69060282HCID 69060282, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 11673727HCID 11673727, compoundYield 34.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(1H-Indazole-3-yl)-(3-methoxyphenyl) methanone (0.406 g, 1.6 mmol) was dissolved in DMF (5 mL) at room temperature. Sodium hydride 95% (0.045 g, 1.9 mmol) was added. When the evolution of hydrogen had stopped, bromo-2-methylpropene (0.324 mL, 3.2 mmol) was added. After the reaction stirred for several minutes, lithium chloride (3.41 g, 80.4 mmol) was added directly to the reaction mixture. The temperature was elevated to 160° C., and stirred for several days. The reaction was monitored my thin layer chromatography. When most of the starting material was gone, the reaction was diluted with water and ethyl acetate. The organic layer was repeatedly extracted with brine to remove DMF. The organic layer was passed through a pad of silica gel, then purified by flash chromatography (silica gel, hexane-EtOAc, 10:1 then 5:1), and crystallized with hexane to yield (3-hydroxyphenyl)[1-(2-methylprop-2-enyl)-1H-indazol-3-yl]methanone (0.160 g) as an off-white solid.

Workup

  1. customwas elevated to 160° C.
  2. stirringstirred for several days
  3. extractionThe organic layer was repeatedly extracted with brine
  4. customto remove DMF
  5. custompurified by flash chromatography (silica gel, hexane-EtOAc, 10:1
  6. custom5:1), and crystallized with hexane

Sources & evidence

ORD record
ord-fa7788b6e6b645a184fcc5e613c94aab
Source dataset
uspto-grants-2009_10
Patent number
US07598286B2

Reaction notes

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