Sodium hydride → HCID 69057692, compound

HRID 1817506Notes

Reaction equation

HRID 1817506 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[CH2:25][CH:26]=[C:27]([CH3:29])[CH3:28].[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]([CH2:25][CH:26]=[C:27]([CH3:29])[CH3:28])[N:2]=2)=[O:11])[CH:17]=[CH:16][CH:15]=1

Participants

9

Reactant 5

HCID 24758Sodium hydrideHCID 700922-Butene, 1-bromo-3-methyl-HCID 433294Lithium ChlorideHCID 69060282HCID 69060282, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 69057692HCID 69057692, compoundYield 27.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(1H-Indazole-3-yl)-(3-methoxyphenyl) methanone (0.406 g, 1.6 mmol, example 14 step A) 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, 4-bromo-2-methyl-2-butene (0.371 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 by 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 column chromatography, and crystallized with hexane to yield (3-hydroxyphenyl)[1-(3-methylbut-2-enyl)-1H-indazol-3-yl]methanone (0.133 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 column chromatography
  6. customcrystallized with hexane

Sources & evidence

ORD record
ord-202d0362147a4a22a986e5c1e8acf1be
Source dataset
uspto-grants-2009_10
Patent number
US07598286B2

Reaction notes

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