Tetrahydrofuran → 1-(6-bromo-5-(2,4-difluorophenoxy)-1H-indazol-1-yl)-2-methylpropan-2-ol

HRID 912474Notes

Reaction equation

HRID 912474 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH2:11][C:12](=[O:14])[CH3:13])=[CH:4][C:3]=1[O:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[F:23].[CH3:24][Mg]Cl.C1COCC1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH2:11][C:12]([CH3:24])([OH:14])[CH3:13])=[CH:4][C:3]=1[O:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[F:23]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 674168791-(6-Bromo-5-(2,4-difluorophenoxy)-1H-indazol-1-yl)propan-2-oneHCID 178418332HCID 178418332, compound

Product 1

HCID 674164781-(6-bromo-5-(2,4-difluorophenoxy)-1H-indazol-1-yl)-2-methylpropan-2-olYield 96%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of 1-(6-Bromo-5-(2,4-difluorophenoxy)-1H-indazol-1-yl)propan-2-one (3.81 g, 10.0 mmol) in toluene (100 mL) at 21° C. was added a 3.0 M solution of methylmagnesium chloride in THF (5.0 mL, 15 mmol) in one portion. The temperature of the resulting solution rose to 34° C. and was stirred without any temperature control. After a total of 60 min the reaction mixture was quenched by addition of saturated ammonium chloride (50 mL). The resulting mixture was vigorously stirred for 20 min, then transferred to a separatory funnel and shaken. The organic layer was dried over sodium sulfate and the solvent removed under reduced pressure to afford the title compound as an orange oil (3.79 g, 96%) that slowly crystallized on standing.

Workup

  1. customrose to 34° C.
  2. customAfter a total of 60 min the reaction mixture was quenched by addition of saturated ammonium chloride (50 mL)
  3. stirringThe resulting mixture was vigorously stirred for 20 min
  4. customtransferred to a separatory funnel
  5. stirringshaken
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-592930c06be24d70b616f07817898905
Source dataset
uspto-grants-2011_09
Patent number
US08026233B2

Reaction notes

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