Dimethylformamide → 3-(1-Propylpiperidin-4-YL)phthalonitrile
Reaction equation
F[C:2]1[C:7](S(C)(=O)=O)=[CH:6][CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][CH3:20])[CH2:14][CH2:13]1.[C-:21]#[N:22].[Na+].C1OCCOCCOCCOCCOCCOC1.C(=O)([O-])[O-].[Na+].[Na+].C[N:49]([CH3:52])C=O>>[CH2:18]([N:15]1[CH2:16][CH2:17][CH:12]([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([C:21]#[N:22])[C:2]=2[C:52]#[N:49])[CH2:13][CH2:14]1)[CH2:19][CH3:20]Participants
6
Procedure
To a solution of 4-[2-fluoro-3-(methylsulfonyl)phenyl]-1-propylpiperidine (0.2 g, 0.67 mmol) in N,N-dimethylformamide (30 ml) was added sodium cyanide (0.82 g, 1.67 mmol) and 18-crown-6-ether (5 mg). The mixture was heated at reflux for 15 h and then brought to ambient temperature. Aqueous sodium carbonate (10%, 50 ml) was added and the phases were separated. The aqueous phase was extracted with ethylacetate (2×50 ml) and the combined organic phases was dried (MgSO4) and evaporated under reduced pressure to give an oil. Purification by flash column chromatography (ethylacetate/methanol, 1:1) gave the title compound: 0.07 g (41%). MS m/z (relative intensity, 70 eV) 253 (M+, 3), 225 (17), 224 (bp), 154 (6), 70 (12).
Workup
- temperatureThe mixture was heated
- temperatureat reflux for 15 h
- custombrought to ambient temperature
- customthe phases were separated
- extractionThe aqueous phase was extracted with ethylacetate (2×50 ml)
- dry with materialthe combined organic phases was dried (MgSO4)
- customevaporated under reduced pressure
- customto give an oil
- customPurification by flash column chromatography (ethylacetate/methanol, 1:1)
Sources & evidence
- ORD record
- ord-34b7a3c691854a1a903513afe0c54765
- Source dataset
- uspto-grants-2012_11
- Patent number
- US08314126B2
Reaction notes
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