Dimethylformamide → 2(1H)-Pyridinone,1-(4-methoxyphenyl)-5-(trifluoromethyl)-

HRID 401505

Reaction equation

[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[CH:5][C:6](=[O:9])[NH:7][CH:8]=1.I[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1.C([O-])([O-])=O.[K+].[K+].CN(C=O)C>N.[Cu]I>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([N:7]2[CH:8]=[C:3]([C:2]([F:1])([F:10])[F:11])[CH:4]=[CH:5][C:6]2=[O:9])=[CH:14][CH:15]=1

Participants

Conditions

Temperature: 135 °C

Procedure

A mixture of 5-(trifloromethyl)-2(1H)-pyridone (815.5 mg, 5 mmol), 4-iodoanisole (2.34 g, 10 mmol), CuI (952 mg, 5 mmol), K2CO3 (691 mg, 5 mmol) and DMF (5 ml) was heated at 135° C. overnight. The reaction mixture was diluted with 10% ammonia (15 ml) and extracted with ethyl acetate. The organic extract was washed with saturated sodium chloride, dried over magnesium sulfate and evaporated. Column chromatography purification (30% ethyl acetate-hexane) afforded 526 mg (39.2%) of 1-(4-methoxyphenyl)-5-(trifloromethyl)-2-pyridone. This compound (268.2 mg, 1 mmol) was treated with 1M BBr3 solution in dichloromethane (DCM, 2 ml) in DCM (5 ml) for 2 hours at 0° C. Reaction mixture was diluted with DCM and washed 3 times with water. Organic phase was dried over sodium sulfate and evaporated. The residue was separated by column chromatography (20% ethyl acetate-DCM) to afford the title compound as an off-white solid, 226 mg (89%). The 1H NMR spectra was consistent with the structure of Compound 10.

Workup

extractionextracted with ethyl acetate
extractionThe organic extract
washwas washed with saturated sodium chloride
dry with materialdried over magnesium sulfate
customevaporated
customColumn chromatography purification (30% ethyl acetate-hexane)

Sources & evidence

ORD record: ord-888f00936297475e8020806961d426d4
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08741936B2

Linked notes

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