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

HRID 2175638Notes

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

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

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

Sources & evidence

ORD record: ord-18368ea57dec40b19baabf701de3b35d
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09062048B2

Reaction notes

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