Potassium Carbonate → 5-(2,4-difluorophenoxy)-1-(2-hydroxy-2-methylpropyl)-1H-indazole-6-carboxylic acid

HRID 912463Notes

Reaction equation

HRID 912463 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH2:11][C:12]([CH3:15])([OH:14])[CH3:13])=[CH:4][C:3]=1[O:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[F:24].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:54](=O)([O-:56])[O-:55].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CO.O>[F:24][C:18]1[CH:19]=[C:20]([F:23])[CH:21]=[CH:22][C:17]=1[O:16][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[C:54]([OH:56])=[O:55])[N:8]([CH2:11][C:12]([OH:14])([CH3:15])[CH3:13])[N:7]=[CH:6]2

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 67416478HCID 67416478, compound

Product 1

HCID 674176645-(2,4-difluorophenoxy)-1-(2-hydroxy-2-methylpropyl)-1H-indazole-6-carboxylic acidYield 44.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
50 °C

Procedure

To a solution of 1-(6-bromo-5-(2,4-difluorophenoxy)-1H-indazol-1-yl)-2-methylpropan-2-ol (0.691 g, 1.74 mmol) in 9:1 methanol/water v/v (11.6 mL) was added palladium (II) acetate (0.0195 g, 0.0870 mmol), 1-((3-(diphenylphosphino)propyl)(phenyl)phosphino)benzene (0.0359 g, 0.0870 mmol), and potassium carbonate (0.721 g, 5.22 mmol). The flask was evacuated and backfilled three times with carbon monoxide, and heated to 50° C. under a carbon monoxide balloon for S hours. The reaction mixture was acidified with 5N HCl and extracted twice with dichloromethane. The organic layer was concentrated, taken up in 5M NaOH, was washed twice with ethyl acetate, and then acidified to pH 1 with HCl. The organic layer was then extracted twice with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and concentrated to yield 5-(2,4-difluorophenoxy)-1-(2-hydroxy-2-methylpropyl)-1H-indazole-6-carboxylic acid (0.280 g, 44.4% yield).

Workup

  1. customThe flask was evacuated
  2. extractionextracted twice with dichloromethane
  3. concentrationThe organic layer was concentrated
  4. washwas washed twice with ethyl acetate
  5. extractionThe organic layer was then extracted twice with ethyl acetate
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-d23092314537432197327166fb2c36fe
Source dataset
uspto-grants-2011_09
Patent number
US08026233B2

Reaction notes

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