Malononitrile → 2-Methoxy-6-oxo-4-(trifluoromethyl)-1,4,5,6-tetrahydropyridine-3-carbonitrile
Reaction equation
[CH3:1][O-:2].[Na+].[C:4](#[N:8])[CH2:5][C:6]#[N:7].[F:9][C:10]([F:18])([F:17])/[CH:11]=[CH:12]/[C:13](OC)=[O:14]>CO>[CH3:1][O:2][C:6]1[NH:7][C:13](=[O:14])[CH2:12][CH:11]([C:10]([F:18])([F:17])[F:9])[C:5]=1[C:4]#[N:8]Participants
Procedure
7.47 g (138.39 mmol) of sodium methoxide in methanol (85 ml) were initially charged with ice cooling, and 6.04 g (91.44 mmol) of malononitrile were added in portions. Subsequently, 11.84 g (76.84 mmol) of methyl 4,4,4-trifluorocrotonate were added dropwise while stirring, and the mixture was stirred at room temperature for 30 min and then heated to reflux for 1 h. Thereafter, the mixture was concentrated to dryness under reduced pressure. The residue was admixed with water and extracted four times with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated. Further purification was effected by chromatography on silica gel (3:1 cyclohexane-ethyl acetate). This gave 1.95 g of the target compound (11% of theory).
Workup
- additionwere added in portions
- stirringthe mixture was stirred at room temperature for 30 min
- temperatureheated
- temperatureto reflux for 1 h
- concentrationThereafter, the mixture was concentrated to dryness under reduced pressure
- extractionextracted four times with ethyl acetate
- dry with materialThe combined organic phases were dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customFurther purification
Sources & evidence
- ORD record
- ord-314c6124f8ed4de78aa9820975093e31
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08765769B2
Reaction notes
Loading…