Boron tribromide → 7-Chloro-1-(3-fluoro-4-hydroxyphenyl)-1H-indazol-4-ol

HRID 2423107Notes

Reaction equation

HRID 2423107 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:26]C)=[C:6]2[C:10]=1[N:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17]CC3C=CC=CC=3)=[C:13]([F:25])[CH:12]=1)[N:8]=[CH:7]2.B(Br)(Br)Br>Br.C(OCC)(=O)C.C([O-])(O)=O.[Na+].O>[Cl:1][C:2]1[C:10]2[N:9]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([F:25])[CH:12]=3)[N:8]=[CH:7][C:6]=2[C:5]([OH:26])=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 25134Boron tribromideHCID 592729677-Chloro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-4-(methyloxy)-1H-indazole

Product 1

HCID 1359103687-Chloro-1-(3-fluoro-4-hydroxyphenyl)-1H-indazol-4-olYield 23.1%

Reagents, catalysts & solvents 3

HCID 260Hydrogen BromideSolventHCID 8857Ethyl AcetateSolventHCID 86585896Sodium bicarbonate waterSolvent

Conditions

Temperature
-78 °C

Procedure

A mixture of 7-chloro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-4-(methyloxy)-1H-indazole (D29) (2.41 g, 6.30 mmol) in 48% hydrobromic acid (120 mL) was heated to reflux and reaction was followed by LC-MS. After 2 hrs, the mixture was concentrated to ˜30 mL on the rotary evaporator and then solid NaHCO3 was added to pH 6. The product was extracted into ethyl acetate and the extracts were dried (Na2SO4) and concentrated. This product was dissolved in dichloromethane (60 mL) and cooled to −78° C. under argon and boron tribromide (2.381 mL, 25.2 mmol) was added dropwise via syringe. After 10 mins at −78° C., the mixture was allowed to reach room temperature and stirring was continued for 24 hrs. The mixture was diluted with ethyl acetate and NaHCO3/water and the pH adjusted to 6 and the product was extracted into ethyl acetate. The extracts were dried (Na2SO4), concentrated and chromatographed (silica, 10% methanol in dichloromethane to crude product that was recolumned by 0-100% ethyl acetate in hexane) to give the title compound as an off-white powder (405 mg) (E14).

Workup

  1. temperaturewas heated
  2. temperatureto reflux
  3. customreaction
  4. concentrationthe mixture was concentrated to ˜30 mL on the rotary evaporator
  5. additionsolid NaHCO3 was added to pH 6
  6. extractionThe product was extracted into ethyl acetate
  7. dry with materialthe extracts were dried (Na2SO4)
  8. concentrationconcentrated
  9. dissolutionThis product was dissolved in dichloromethane (60 mL)
  10. waitAfter 10 mins at −78° C.
  11. customto reach room temperature
  12. waitwas continued for 24 hrs
  13. extractionthe product was extracted into ethyl acetate
  14. dry with materialThe extracts were dried (Na2SO4)
  15. concentrationconcentrated
  16. customchromatographed (silica, 10% methanol in dichloromethane to crude product that was recolumned by 0-100% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-0cad6ea5a9dd4503a612fd134e184c93
Source dataset
uspto-grants-2011_06
Patent number
US07960563B2

Reaction notes

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