Hydrogen Peroxide → 5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazol-6-ol

HRID 1897471Notes

Reaction equation

HRID 1897471 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH2:11][CH:12]([CH3:14])[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].C([Li])CCC.C[O:30]B(OC)OC.[OH-].[Na+].OO>CCOCC.O>[F:23][C:17]1[CH:18]=[C:19]([F:22])[CH:20]=[CH:21][C:16]=1[O:15][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[OH:30])[N:8]([CH2:11][CH:12]([CH3:14])[CH3:13])[N:7]=[CH:6]2

Participants

8

Reactant 5

HCID 784Hydrogen Peroxide2×HCID 8470Trimethyl borateHCID 14798Sodium Hydroxide3×HCID 574187626-Bromo-5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole2×HCID 178418339Butyllithium

Product 1

HCID 1361636625-(2,4-difluorophenoxy)-1-isobutyl-1H-indazol-6-olYield 41%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolvent2×

Procedure

(15d; prepared according to Example 110, Steps A-E: 6-Bromo-5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole (1.36 g, 3.6 mmol) was dissolved in dry ether (17.5 mL) and cooled to −78° C. n-Butyl lithium (1.7 mL of 2.5 M in hexane) was added dropwise over 10 minutes and the mixture was stirred for 30 minutes. Trimethylborate (6 mL, 53.5 mmol) was added drop-wise over 10 minutes and the reaction mixture was allowed to warm to room temperature and stir for 18 hours. The mixture was cooled to −10° C. and 2N NaOH (3.6 mL) and water (3 mL) were added followed by H2O2 (3.6 mL) and 2N NaOH (3.6 mL). The reaction mixture was stirred at room temperature for 2 hours when white precipitate formed. Water (3 mL), 4N NaOH (4 mL), and H2O2 (1 mL) was added and the mixture stirred for another 20 minutes. The mixture was then diluted with ether and the layers separated. The aqueous layer was washed with ether, acidified and then extracted with ether (2×). The combined ether extracts were washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure to afford 0.465 g product (41% yield).

Workup

  1. customprepared
  2. additionwas added dropwise over 10 minutes
  3. stirringstir for 18 hours
  4. temperatureThe mixture was cooled to −10° C.
  5. stirringThe reaction mixture was stirred at room temperature for 2 hours when white precipitate
  6. customformed
  7. stirringthe mixture stirred for another 20 minutes
  8. customthe layers separated
  9. washThe aqueous layer was washed with ether
  10. extractionextracted with ether (2×)
  11. washThe combined ether extracts were washed with water and brine
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-aa0d9c55db4a4b6783de887587762565
Source dataset
uspto-grants-2013_08
Patent number
US08518983B2

Reaction notes

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