Boron tribromide → HCID 136085247, compound

HRID 2423111Notes

Reaction equation

HRID 2423111 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([N:10]2[C:18]3[C:13](=[C:14]([O:19]CC4C=CC=CC=4)[CH:15]=[CH:16][CH:17]=3)[CH:12]=[N:11]2)[CH:5]=[CH:6][C:7]=1[O:8]C.B(Br)(Br)Br>C(Cl)Cl>[OH:8][C:7]1[CH:6]=[CH:5][C:4]([N:10]2[C:18]3[CH:17]=[CH:16][CH:15]=[C:14]([OH:19])[C:13]=3[CH:12]=[N:11]2)=[CH:3][C:2]=1[CH3:1]

Participants

4

Reactant 2

HCID 25134Boron tribromide2×HCID 59272963HCID 59272963, compound

Product 1

HCID 136085247HCID 136085247, compoundYield 9.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

1-[3-Methyl-4-(methyloxy)phenyl]-4-[(phenylmethyl)oxy]-1H-indazole (D34) (550 mg, 1.64 mmol) was dissolved in dry DCM (20 mL) and degassed by sonication under a flow of argon. The solution was cooled to −78° C. and after 10 mins treated with BBr3 (1M in DCM, 3.29 mL, 3.29 mmol) 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 45 minutes more BBr3 (1M in DCM, 3.29 mL, 3.29 mmol) was added to the mixture and after 17 hours it was partitioned between DCM (75 mL)/water (75 mL), the pH adjusted to 7 by addition of a solution of NaHCO3 and the layers separated. The aqueous phase was extracted with DCM (2×50 mL) twice and the combined organics were washed with brine (50 mL) and dried over MgSO4, filtered and concentrated in vacuo. The crude material (456 mg) was purified by flash chromatography (Biotage SP4) with a gradient of EtOAc 0 to 40% in hexane. The isolated material was further purified by MDAP to afford 36 mg of the title compound (E18).

Workup

  1. customdegassed by sonication under a flow of argon
  2. additionwhen the addition
  3. customwas removed
  4. customto reach room temperature
  5. customwas partitioned between DCM (75 mL)/water (75 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 DCM (2×50 mL) twice
  9. washthe combined organics were washed with brine (50 mL)
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe crude material (456 mg) was purified by flash chromatography (Biotage SP4) with a gradient of EtOAc 0 to 40% in hexane
  14. customThe isolated material was further purified by MDAP

Sources & evidence

ORD record
ord-e3fc4abfcc414e48b2a4f86313fb7d2c
Source dataset
uspto-grants-2011_06
Patent number
US07960563B2

Reaction notes

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