Dimethylformamide → HCID 22499493, compound
Reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.Cl[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([CH3:24])[C:19]=1C#N.C[N:28](C=O)C>>[C:24]([C:20]1[CH:19]=[C:18]([O:3][CH:4]2[CH2:5][CH2:6][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:8][CH2:9]2)[CH:23]=[CH:22][N:21]=1)#[N:28]Participants
5
Procedure
NaH (60% in mineral oil, 303 mg, 7.6 mmol) in 15 mL of DMF was stirred at rt in a round-bottom flask. tert-Butyl 4-hydroxypiperidine-1-carboxylate (1.42 g, 7.0 mmol) was added in portions and the resulting mixture was stirred at rt for 30 min. 4-Chlorocyanopicoline (750 mg, 5.4 mmol) in 5 mL of DMF was added dropwise. After stirring at rt for 1 h, LC-MS indicated that the reaction was complete. The reaction mixture was then partitioned between EtOAc (30 mL) and water (25 mL). The organic layer was washed with brine (10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to give an oil which was purified by silica gel flash chromatography, eluting with 0-20% EtOAc in hexanes, to give tert-butyl 4-(2-cyanopyridin-4-yloxy)piperidine-1-carboxylate (1.2 g, 71%) as a light yellow oil. LC-MS (ESI) m/z 304 (M+H)+.