Hydrochloric Acid → 4,4,4-trifluoro-1-(2-methoxyphenyl)butane-1,3-dione

HRID 2178657Notes

Reaction equation

[H-].[Na+].[F:3][C:4]([F:11])([F:10])[C:5]([O:7]CC)=O.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20](=[O:22])[CH3:21].Cl>COCCOC>[F:11][C:4]([F:3])([F:10])[C:5](=[O:7])[CH2:21][C:20]([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[O:13][CH3:12])=[O:22]

Participants

Conditions

Temperature: 160 °C

Procedure

To a suspension of sodium hydride (60% in mineral oil, 202 mg, 8.0 mmol) in 1,2-dimethoxyethane (4 mL) was added drop-wise ethyl trifluoroacetate (954 μL, 8.0 mmol) followed by 1-(2-methoxyphenyl)ethanone (552 μL, 4.0 mmol) and the reaction was heated to 160° C. in a microwave for 15 minutes. Aqueous hydrochloric acid (1 N, 20 mL) was added and the mixture was extracted with tert-butyl methyl ether (3×10 mL). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 0% to 10% tert-butyl methyl ether in heptanes) afforded the title compound as a red solid. Yield: 933 mg, 3.79 mmol, 95%. GCMS m/z 246 (M+). 1H NMR (400 MHz, CDCl3) δ 3.96 (s, 3H), 6.99 (s, 1H), 7.02 (br d, J=8.5 Hz, 1H), 7.08 (ddd, J=8, 7, 1.0 Hz, 1H), 7.55 (ddd, J=8.4, 7.4, 1.8 Hz, 1H), 7.99 (dd, J=7.9, 1.9 Hz, 1H).

Workup

extractionthe mixture was extracted with tert-butyl methyl ether (3×10 mL)
dry with materialThe combined organic layers were dried over sodium sulfate
concentrationconcentrated in vacuo
customPurification via silica gel chromatography (Gradient: 0% to 10% tert-butyl methyl ether in heptanes)

Sources & evidence

ORD record: ord-f7bac20b9ef84dfaa8850cbf9cda3c9e
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09067934B2

Reaction notes

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