4-Phenylpiperidine → Tert-butyl 3-cyano-3-(4-phenylpiperidin-1-yl)pyrrolidine-1-carboxylate
Reaction equation
O=[C:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.[C:14]1([CH:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[C-:26]#[N:27].C([Al+]CC)C>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:26]([C:2]1([N:23]2[CH2:22][CH2:21][CH:20]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:25][CH2:24]2)[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1)#[N:27]Participants
Procedure
A mixture of tert-butyl 3-oxopyrrolidine-1-carboxylate (0.91 g, 4.9 mmol), 4-phenylpiperidine (0.792 g, 4.91 mmol) and titanium (IV) isopropoxide (1.39 g, 4.91 mmol) was stirred at room temperature for about 16 h. Diethylaluminum cyanide solution (1M in DCE, 9.82 mL) was added and the reaction mixture was stirred for about 4 hours then quenched by the dropwise addition of saturated aqueous sodium bicarbonate solution. The reaction mixture was filtered and the layers separated. The organic phase was washed with saturated aqueous sodium bicarbonate (50 mL) and brine (50 mL), dried over magnesium sulfate and concentrated under reduced pressure to yield tert-butyl 3-cyano-3-(4-phenylpiperidin-1-yl)pyrrolidine-1-carboxylate (1.2 g, 3.38 mmol) as a yellow oil. HPLC (Table 1, Method f) Rt 6.03 min; m/z: (M+H)+ 356.
Workup
- stirringthe reaction mixture was stirred for about 4 hours
- customthen quenched by the dropwise addition of saturated aqueous sodium bicarbonate solution
- filtrationThe reaction mixture was filtered
- customthe layers separated
- washThe organic phase was washed with saturated aqueous sodium bicarbonate (50 mL) and brine (50 mL)
- dry with materialdried over magnesium sulfate
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-696c2de8d2d94647a7267de0ce66062b
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08754107B2
Reaction notes
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