Potassium Fluoride → 1-Chloro-7-(trifluoromethyl)isoquinoline

HRID 1896961Notes

Reaction equation

HRID 1896961 reaction equation
[F-].[K+].C[Si](C)(C)[C:5]([F:8])([F:7])[F:6].[Cl:11][C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19](I)[CH:20]=2)[CH:15]=[CH:14][N:13]=1>CN1C(=O)CCC1.C(OCC)(=O)C.[Cu]I>[Cl:11][C:12]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([C:5]([F:8])([F:7])[F:6])[CH:20]=2)[CH:15]=[CH:14][N:13]=1

Participants

7

Reactant 3

HCID 522689Potassium FluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 441563091-Chloro-7-iodoisoquinoline

Product 1

HCID 585626771-Chloro-7-(trifluoromethyl)isoquinoline

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
120 °C

Procedure

Into a 8 mL sealed tube, was placed potassium fluoride (300 mg, 5.17 mmol, 6.00 equiv, 100%), copper(I) iodide (900 mg, 4.66 mmol, 5.50 equiv, 100%), trimethyl(trifluoromethyl)silane (720 mg, 5.07 mmol, 5.00 equiv, 100%), NMP (3 mL, 100%) and a solution of 1-chloro-7-iodoisoquinoline (as prepared in the previous step, 250 mg, 0.86 mmol, 1.00 equiv, 100%) in NMP (1 mL). The reaction mixture was stirred for 12 h at 120° C. in an oil bath. The resulting mixture was diluted with 20 mL of ethyl acetate, washed with 3×10 mL of saturated solution of KI, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by chromatography over a silica gel column with ethyl acetate:petroleum ether (1:50). The title compound was obtained as a yellow solid.

Workup

  1. customInto a 8 mL sealed tube
  2. washwashed with 3×10 mL of saturated solution of KI
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by chromatography over a silica gel column with ethyl acetate:petroleum ether (1:50)

Sources & evidence

ORD record
ord-17ea61b629524fd187cdccd5f9e90c0c
Source dataset
uspto-grants-2013_08
Patent number
US08518969B2

Reaction notes

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