Reaction equation
[H-].[Na+].[F:3][C:4]([F:15])([F:14])[C:5]1[CH:10]=[CH:9][C:8]([C:11](=[O:13])[CH3:12])=[CH:7][CH:6]=1.[CH2:16]([O:18][C:19](=[O:25])[C:20](OCC)=[O:21])[CH3:17]>CN(C=O)C>[CH2:16]([O:18][C:19](=[O:25])[C:20](=[O:21])[CH2:12][C:11](=[O:13])[C:8]1[CH:7]=[CH:6][C:5]([C:4]([F:14])([F:15])[F:3])=[CH:10][CH:9]=1)[CH3:17]Participants
Conditions
- Temperature
- 45 °C
Procedure
Sodium hydride (1.6 g, 63.7 mmol, 95%) was added to a solution of 1-(4-trifluoromethyl-phenyl)-ethanone (10.0 g, 53.1 mmol) and oxalic acid diethyl ester (8.7 mL, 63.7 mmol) in 75 mL dry DMF at 0° C. The reaction was allowed to come to room temperature and then heated to 45° C. for 45 minutes. The reaction was then cooled, concentrated in vacuo, and the residue taken up in EtOAc. The organic layer was then washed with 2 M HCl (1×100 mL), dried (Na2SO4) and the solvent removed in vacuo. Purification by flash column chromatography (gradient elution: 5% EtOAc/hexane to 55% EtOAc/hexane) gave the intermediate 2,4-dioxo-4-(4-trifluoromethyl-phenyl)-butyric acid ethyl ester (12.2 g, 80%) which was then taken up in EtOH and refluxed in the presence of hydroxylamine hydrochloride (10.2 g, 132.3 mmol) for 3H. The reaction was then cooled, diluted with EtOAc, washed with dilute NaHCO3, brine, dried (Na2SO4), and concentrated in vacuo. Recrystallization from EtOAc/hexane gave 5.2 g of the title compound. MS m/z 286 (M+1).
Workup
- customto come to room temperature
- temperatureThe reaction was then cooled
- concentrationconcentrated in vacuo
- washThe organic layer was then washed with 2 M HCl (1×100 mL)
- dry with materialdried (Na2SO4)
- customthe solvent removed in vacuo
- customPurification
- washby flash column chromatography (gradient elution: 5% EtOAc/hexane to 55% EtOAc/hexane)
Sources & evidence
- ORD record
- ord-6f389044264346f8b3e8a6144062e7ac
- Source dataset
- uspto-grants-2007_07
- Patent number
- US07244763B2
Linked notes
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