Methanesulfonic Acid → 6-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-5-ol

HRID 1661976Notes

Reaction equation

HRID 1661976 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][C:3]=1[OH:11].[CH2:12]1[CH2:17][O:16][CH:15]=[CH:14][CH2:13]1.CS(O)(=O)=O>C1COCC1>[Br:1][C:2]1[C:3]([OH:11])=[CH:4][C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH:15]1[CH2:14][CH2:13][CH2:12][CH2:17][O:16]1)[CH:6]=2

Participants

5

Reactant 3

HCID 6395Methanesulfonic AcidHCID 80803,4-dihydro-2H-pyranHCID 591599466-Bromo-1H-indazol-5-ol

Product 1

HCID 667670386-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-5-olYield 162.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-bromo-5-hydroxy-1H-indazole (725.0 g, 3.4 mol) in THF (10.2 L) is added DHP (336.5 mL, 3.57 mol) and CH3SO3H (65.4 g, 0.68 mol) at RT. The resulting mixture is stirred at RT for 22 hours. The reaction mixture is quenched with distilled water (6 L) and extracted with EtOAc (6 L). Saturated aqueous NaHCO3 solution (1100 mL) is added to adjust the pH to 8. After phase separation, the organic phase is washed with water (4 L) and then saturated aqueous sodium chloride (3 L), dried over anhydrous Na2SO4, filtered, and concentrated to give the product as a solid (1.64 kg, 99.3% yield). MS (m/z): 299.0 (M+H).

Workup

  1. customThe reaction mixture is quenched with distilled water (6 L)
  2. extractionextracted with EtOAc (6 L)
  3. additionSaturated aqueous NaHCO3 solution (1100 mL) is added
  4. customAfter phase separation
  5. washthe organic phase is washed with water (4 L)
  6. dry with materialsaturated aqueous sodium chloride (3 L), dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-922ce42faf4f472282576bf6eff402d8
Source dataset
uspto-grants-2011_10
Patent number
US08030302B2

Reaction notes

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