Nitric Acid → HCID 59280056, compound

HRID 1518161Notes

Reaction equation

HRID 1518161 reaction equation
[Cl:1][C:2]1[C:3]([NH2:19])=[CH:4][C:5]([CH3:18])=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]([F:17])([F:16])[F:15])[CH:7]=1.[C:20]([O:23]C(=O)C)(=O)[CH3:21].[N+:27]([O-])([OH:29])=[O:28]>CC(O)=O>[Cl:1][C:2]1[C:3]([NH:19][C:20](=[O:23])[CH3:21])=[C:4]([N+:27]([O-:29])=[O:28])[C:5]([CH3:18])=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]([F:16])([F:17])[F:15])[CH:7]=1

Participants

5

Reactant 3

HCID 944Nitric AcidHCID 7918Acetic Anhydride2×HCID 59280099HCID 59280099, compound

Product 1

HCID 59280056HCID 59280056, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

5-Chloro-2-methyl-2′-trifluoromethyl-biphenyl-4-ylamine (384 mg, 1.34 mmol, as prepared in the previous step) was placed in a 50 mL round-bottom flask equipped with a magnetic stir bar. Acetic anhydride (1.5 mL) was added. The mixture was stirred at rt for 1 h and then cooled to 0° C. To a 4 mL vial cooled at 0° C. was added AcOH (0.27 mL), acetic anhydride (0.31 mL), and nitric acid (0.45 mL). The nitrating mixture was added dropwise via pipette to the above-prepared solution, maintaining the temperature below 10° C. Upon completion of the addition, the mixture was stirred at 0° C. for 1 hour and poured onto ice. The resulting precipitate was isolated by filtration, washed with water, and dissolved in EtOAc. The solution was dried over MgSO4 and filtered, and the solvent was removed under reduced pressure. The residue was purified by column chromatography using a 40-g SiO2 pre-packed column eluting with EtOAc/hexanes, 0:1 to 3:7, v/v over 30 min, yielding 301 mg (60%) of the title compound. 1H-NMR (400 MHz, CDCl3) δ: 7.80 (d, J=7.8 Hz, 1H), 7.54-7.68 (m, 2H), 7.50 (s, 1H), 7.43 (s, 1H), 7.25 (d, J=7.6 Hz, 1H), 2.21 (s, 3H), 1.98 (s, 3H).

Workup

  1. customwas placed in a 50 mL round-bottom flask
  2. customequipped with a magnetic stir bar
  3. temperaturecooled to 0° C
  4. temperatureTo a 4 mL vial cooled at 0° C.
  5. additionThe nitrating mixture was added dropwise via pipette to the above-prepared solution
  6. temperaturemaintaining the temperature below 10° C
  7. additionUpon completion of the addition
  8. stirringthe mixture was stirred at 0° C. for 1 hour
  9. additionpoured onto ice
  10. customThe resulting precipitate was isolated by filtration
  11. washwashed with water
  12. dissolutiondissolved in EtOAc
  13. dry with materialThe solution was dried over MgSO4
  14. filtrationfiltered
  15. customthe solvent was removed under reduced pressure
  16. customThe residue was purified by column chromatography
  17. washeluting with EtOAc/hexanes, 0:1 to 3:7, v/v over 30 min

Sources & evidence

ORD record
ord-81efbe40e37444ef9079df13bbffab3d
Source dataset
uspto-grants-2012_07
Patent number
US08232409B2

Reaction notes

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