7-Acetyl-5-methylquinolin-8-yl trifluoromethanesulfonate → 1-[8-(3-Fluorophenyl)-5-methylquinolin-7-yl]ethanone

HRID 1192561Notes

Reaction equation

FC(F)(F)S(O[C:7]1[C:8]([C:18](=[O:20])[CH3:19])=[CH:9][C:10]([CH3:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.[F:23][C:24]1[CH:25]=[C:26]([Zn]I)[CH:27]=[CH:28][CH:29]=1>O1CCCC1>[F:23][C:24]1[CH:29]=[C:28]([C:7]2[C:8]([C:18](=[O:20])[CH3:19])=[CH:9][C:10]([CH3:17])=[C:11]3[C:16]=2[N:15]=[CH:14][CH:13]=[CH:12]3)[CH:27]=[CH:26][CH:25]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a mixture of 7-acetyl-5-methylquinolin-8-yl trifluoromethanesulfonate (0.833 g, 2.50 mmol) in tetrahydrofuran (20 mL), with stirring, was added 0.5 M (3-fluorophenyl)(iodo)zinc in THF (10.0 mL, 5.0 mmol), followed by tetrahydrofurantetrakis(triphenylphosphine)palladium(0) (289 mg, 0.250 mmol). The reaction mixture was heated at 60° C. overnight, cooled to room temperature and quenched with sat. sodium bicarbonate. The mixture was filtered through a Celite pad. The filtrate was extracted with ethyl acetate. The combined organic layers were washed with brine, dried and concentrated under reduced pressure. The residue was purified on silica gel, eluting with 0 to 80% ethyl acetate in hexane, to give the desired product (0.379 g, 54%). LCMS calculated for C18H14FNO (M+H)+: m/z=280.1; Found: 280.0.

Workup

temperaturecooled to room temperature
customquenched with sat. sodium bicarbonate
filtrationThe mixture was filtered through a Celite pad
extractionThe filtrate was extracted with ethyl acetate
washThe combined organic layers were washed with brine
customdried
concentrationconcentrated under reduced pressure
customThe residue was purified on silica gel
washeluting with 0 to 80% ethyl acetate in hexane

Sources & evidence

ORD record: ord-b9deb54eb05a4b2c9bd0be7fc3704985
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680108B2

Reaction notes

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