3-(Trifluoromethyl)phenol → 5-Nitro-1-(3-(trifluoromethyl)phenoxy)isoquinoline

HRID 1469722Notes

Reaction equation

HRID 1469722 reaction equation
Cl[C:2]1[C:11]2[C:6](=[C:7]([N+:12]([O-:14])=[O:13])[CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[F:15][C:16]([F:25])([F:24])[C:17]1[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>CC#N.O>[N+:12]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[CH:5]=[CH:4][N:3]=[C:2]2[O:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([C:16]([F:15])([F:24])[F:25])[CH:18]=1)([O-:14])=[O:13]

Participants

6

Reactant 3

HCID 73763-(Trifluoromethyl)phenolHCID 11430Potassium CarbonateHCID 4597741-Chloro-5-nitroisoquinoline

Product 1

HCID 866922295-Nitro-1-(3-(trifluoromethyl)phenoxy)isoquinolineYield 374%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 1-chloro-5-nitroisoquinoline (Step-1, Intermediate-1, 200 mg, 0.96 mmol) in CH3CN (2 mL) were added 3-(trifluoromethyl)phenol (233 mg, 1.4 mmol) and K2CO3 (265 mg, 1.92 mmol). The reaction mass was heated at reflux for 5 h and it was diluted with water and extracted with chloroform. The organic layer was separated, dried, filtered and concentrated. The residue was purified by column chromatography to afford 1.2 g of the title product. 1H NMR (300 MHz, DMSO d6): δ 8.82 (d, J=8.4 Hz, 1H), 8.58 (d, J=7.8 Hz, 1H), 8.17 (s, 2H), 7.76 (t, J=8.4 Hz, 1H), 7.61-7.47 (m, 4H); MS (m/z): 335.12 (M+H)+.

Workup

  1. temperatureThe reaction mass was heated
  2. temperatureat reflux for 5 h
  3. extractionextracted with chloroform
  4. customThe organic layer was separated
  5. customdried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-3614ffc3cb5e49a5b5a7eb3bd258b6a9
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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