4-Bromo-2-methylaniline → 5-bromo-1H-indazole

HRID 908318Notes

Reaction equation

HRID 908318 reaction equation
[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([CH3:9])[CH:3]=1.[H+].[B-](F)(F)(F)F.[N:16]([O-])=O.[Na+].CC([O-])=O.[K+]>O.C(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:7][CH:8]=1)[NH:6][N:16]=[CH:9]2

Participants

7

Reactant 4

HCID 114234-Bromo-2-methylanilineHCID 28118Tetrafluoroboric acidHCID 517044Potassium AcetateHCID 23668193Sodium Nitrite

Product 1

HCID 7619295-bromo-1H-indazoleYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6212ChloroformSolvent

Procedure

4-bromo-2-methylaniline (5.0 g, 27 mmol) was added to a mixture of water (12.3 ml) and HBF4 (48% by weight in water, 12.3 ml, 67 mmol) in a Nalger reaction vessel cooled in an ice water bath. Then, NaNO2 (1.85 g, 27 mmol) in water (3.8 ml) was added while maintaining the temperature of the reaction around 10 C. After 15 minutes, the was then recooled in an ice water bath and filtered via a Buchner funnel. The solid was washed with cold 5% aqueous HBF4, cold MeOH (20 ml) and diethyl ether (3×10 ml). The solid was dried on a Buchner funnel for 1 hour and then added to a flask containing KOAc (5.3 g, 54 mmol, dried in vacuo overnight) and 18-c-6 (0.35 g, 1.3 mmol) suspended in chloroform (250 ml). The reaction was stirred at room temperature for 2 hours and then filtered, and the solid was washed with chloroform. The filtrate was washed with water and brine, dried over sodium sulfate, filtered, concentrated, and diluted with water (250 ml). The suspension was filtered, and the solid was washed with hexanes (50 ml) and diethyl ether (50 ml), collected, and dried in vacuo to give title compound (3.6 g, 68%). MS (ESI pos. ion) m/z: 197 (M+H). Calc'd Exact Mass for C7H5BrN2: 196.

Workup

  1. temperaturecooled in an ice water bath
  2. temperaturewhile maintaining
  3. customthe temperature of the reaction around 10 C
  4. customthe was then recooled in an ice water bath
  5. filtrationfiltered via a Buchner funnel
  6. washThe solid was washed with cold 5% aqueous HBF4, cold MeOH (20 ml) and diethyl ether (3×10 ml)
  7. customThe solid was dried on a Buchner funnel for 1 hour
  8. additionadded to a flask
  9. filtrationfiltered
  10. washthe solid was washed with chloroform
  11. washThe filtrate was washed with water and brine
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated
  15. additiondiluted with water (250 ml)
  16. filtrationThe suspension was filtered
  17. washthe solid was washed with hexanes (50 ml) and diethyl ether (50 ml)
  18. customcollected
  19. customdried in vacuo

Sources & evidence

ORD record
ord-1aee09fb8e1644e6a725b84157ef7be0
Source dataset
uspto-grants-2011_09
Patent number
US08017601B2

Reaction notes

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