Sodium hydride → Tert-butyl 4-(3-bromopyridin-2-yl)-4-cyanopiperidine-1-carboxylate
Reaction equation
[Br:1][C:2]1[C:3]([CH2:8][C:9]#[N:10])=[N:4][CH:5]=[CH:6][CH:7]=1.Cl[CH2:12][CH2:13][N:14]([CH2:22][CH2:23]Cl)[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18].[H-].[Na+]>CS(C)=O.ClCCl>[Br:1][C:2]1[C:3]([C:8]2([C:9]#[N:10])[CH2:23][CH2:22][N:14]([C:15]([O:16][C:17]([CH3:19])([CH3:18])[CH3:20])=[O:21])[CH2:13][CH2:12]2)=[N:4][CH:5]=[CH:6][CH:7]=1Participants
6
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 18 °C
Procedure
The (3-bromopyridin-2-yl)acetonitrile (2.00 g, 10.2 mmol) and tert-butyl bis(2-chloroethyl)carbamate (2.46 g, 10.2 mmol) were dissolved in 102 mL of DMSO. The reaction was purged with a stream of nitrogen and cooled to 18° C. To this reaction was added sodium hydride (0.564 g, 22.3 mmol), which was then warmed to 50° C. and stirred for 18 hours. The mixture was diluted with dichloromethane (150 mL), washed with water (3×150 mL), and partitioned between water and dichloromethane. The organic layer was dried over sodium sulfate, filtered, concentrated, and subjected to silica gel chromatography eluting with 5-30% EtOAc in hexanes to yield tert-butyl 4-(3-bromopyridin-2-yl)-4-cyanopiperidine-1-carboxylate.
Workup
- customThe reaction was purged with a stream of nitrogen
- temperaturewas then warmed to 50° C.
- washwashed with water (3×150 mL)
- custompartitioned between water and dichloromethane
- dry with materialThe organic layer was dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- washeluting with 5-30% EtOAc in hexanes
Sources & evidence
- ORD record
- ord-ada3ebf19805458e9e9bce69da2df3f6
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08258135B2
Reaction notes
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