Boron tribromide → 1-(4-Hydroxyphenyl)-1H-indazol-4-ol

HRID 2423109Notes

Reaction equation

HRID 2423109 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:17]3[C:12](=[C:13]([O:18]CC4C=CC=CC=4)[CH:14]=[CH:15][CH:16]=3)[CH:11]=[N:10]2)=[CH:5][CH:4]=1.B(Br)(Br)Br>C(Cl)Cl>[OH:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:17]3[CH:16]=[CH:15][CH:14]=[C:13]([OH:18])[C:12]=3[CH:11]=[N:10]2)=[CH:7][CH:8]=1

Participants

4

Reactant 2

HCID 25134Boron tribromide2×HCID 592729721-(4-Methoxyphenyl)-4-(phenylmethoxy)-1H-indazole

Product 1

HCID 1359103801-(4-Hydroxyphenyl)-1H-indazol-4-olYield 58.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

1-[4-(Methyloxy)phenyl]-4-[(phenylmethyl)oxy]-1H-indazole (D32) (40 mg, 0.121 mmol) was dissolved in dry DCM (1.5 mL) under argon and cooled to −78° C. in a dry ice-acetone bath. After 5 minutes BBr3 (1M in DCM, 0.242 mL, 0.242 mmol) was added dropwise and when the addition was complete the bath was removed and it was allowed to reach room temperature. The reaction was followed by LC-MS. After 4 hours more BBr3 (1M in DCM, 0.242 mL, 0.242 mmol) was added to the mixture and after 21 hours it was concentrated in vacuo. The residue was partitioned between EtOAc (25 mL)/water (25 mL), the pH adjusted to 7 by addition of a solution of NaHCO3 and the layers separated. The aqueous phase was extracted with EtOAc (2×25 mL) and the combined organics were dried over MgSO4, filtered and concentrated in vacuo. The crude material (28 mg) was purified by flash chromatography (Biotage SP4) with a gradient of EtOAc 30 to 60% in hexane. The isolated material (28 mg) was further purified by MDAP to afford 16 mg of the title compound (E16).

Workup

  1. additionwhen the addition
  2. customwas removed
  3. customto reach room temperature
  4. concentrationwas concentrated in vacuo
  5. customThe residue was partitioned between EtOAc (25 mL)/water (25 mL)
  6. additionthe pH adjusted to 7 by addition of a solution of NaHCO3
  7. customthe layers separated
  8. extractionThe aqueous phase was extracted with EtOAc (2×25 mL)
  9. dry with materialthe combined organics were dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude material (28 mg) was purified by flash chromatography (Biotage SP4) with a gradient of EtOAc 30 to 60% in hexane
  13. customThe isolated material (28 mg) was further purified by MDAP

Sources & evidence

ORD record
ord-fd36fc3615934790b5b7d4c95cd55b52
Source dataset
uspto-grants-2011_06
Patent number
US07960563B2

Reaction notes

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