Acetic Anhydride → 5-bromo-3-cyano-2-(4-fluorophenyl)-6-nitro-2H-indazole 1-oxide

HRID 595699Notes

Reaction equation

HRID 595699 reaction equation
[Br:1][C:2]1[C:3]([N+:13]([O-:15])=[O:14])=[CH:4][C:5]([N+:10]([O-:12])=O)=[C:6]([CH:9]=1)[CH:7]=O.[F:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][CH:18]=1.[C-:24]#[N:25].[Na+].C(OC(=O)C)(=O)C>C(O)(=O)C>[Br:1][C:2]1[C:3]([N+:13]([O-:15])=[O:14])=[CH:4][C:5]2[C:6](=[C:7]([C:24]#[N:25])[N:21]([C:20]3[CH:22]=[CH:23][C:17]([F:16])=[CH:18][CH:19]=3)[N+:10]=2[O-:12])[CH:9]=1

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8929Sodium Cyanide2×HCID 97314-FluoroanilineHCID 772315365-Bromo-2,4-dinitrobenzaldehyde

Product 1

HCID 903325645-bromo-3-cyano-2-(4-fluorophenyl)-6-nitro-2H-indazole 1-oxideYield 56%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred suspension of 5-bromo-2,4-dinitrobenzaldehyde (6.5 g, 0.024 mol) in acetic acid (120 mL) was added 4-fluoroaniline (9.28 g, 0.054 mol) and the reaction mixture was heated to 60° C. to get a clear solution. To this was added sodium cyanide portionwise (6.0 g, 0.123 mol) and the reaction mixture was stirred at 60° C. for 5 min. Acetic anhydride (1.9 mL, 0.020 mol) was added and the reaction mixture was stirred for 5 min at the same temperature. Sodium cyanide (6.0 g, 0.123 mol) was then added at the same temperature at which time the product precipitated out. After stirring for 30 min, the mixture was cooled to RT, diluted with water (50 mL), filtered and washed with ethanol to afford crude product, which was purified by flash column chromatography eluting with PE/EtOAc (100/1) to give pure 5-bromo-3-cyano-2-(4-fluorophenyl)-6-nitro-2H-indazole 1-oxide (5.0 g, 56%). 1H-NMR (CDCl3, 400 MHz) δ 8.40 (s, 1H), 8.15 (s, 1H), 7.67˜7.70 (m, 2H), 7.38˜7.42 (m, 2H). MS (M+H)+: 377/379.

Workup

  1. customto get a clear solution
  2. stirringthe reaction mixture was stirred for 5 min at the same temperature
  3. customprecipitated out
  4. stirringAfter stirring for 30 min
  5. temperaturethe mixture was cooled to RT
  6. additiondiluted with water (50 mL)
  7. filtrationfiltered
  8. washwashed with ethanol
  9. customto afford crude product, which
  10. customwas purified by flash column chromatography
  11. washeluting with PE/EtOAc (100/1)

Sources & evidence

ORD record
ord-386009c1f445453dad9ae77c84dcfaad
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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