Morpholine → 4-(5-Bromopyridin-2-yl)-1-(2-hydroxy-2-methylpropyl)piperidine-4-carbonitrile
Reaction equation
N1CCOCC1.[CH3:7][C:8]1([O:11][CH2:10]1)[CH3:9].[Br:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]2([C:25]#[N:26])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[N:17][CH:18]=1.C(=O)(O)[O-].[Na+]>O>[Br:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]2([C:25]#[N:26])[CH2:20][CH2:21][N:22]([CH2:10][C:8]([OH:11])([CH3:9])[CH3:7])[CH2:23][CH2:24]2)=[N:17][CH:18]=1Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 100 °C
Procedure
Morpholine (catalytic amount) and isobutylene oxide (2.84 g) were added to 4-(5-bromopyridin-2-yl)piperidine-4-carbonitrile (3.4 g) of Reference Example 88(2) and water (35 ml), and the mixture was stirred at 100° C. for 4.5 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction solution and extracted with ethyl acetate. The organic layer was washed with saturated brine dried over anhydrous sodium sulfate and concentrated in vacuo. Water was added to the residue and the precipitated solid was washed with water to give 4-(5-bromopyridin-2-yl)-1-(2-hydroxy-2-methylpropyl)piperidine-4-carbonitrile (3.95 g) as a light brown solid.
Workup
- extractionextracted with ethyl acetate
- washThe organic layer was washed with saturated brine
- dry with materialdried over anhydrous sodium sulfate
- concentrationconcentrated in vacuo
- additionWater was added to the residue
- washthe precipitated solid was washed with water
Sources & evidence
- ORD record
- ord-df13d159f7a14546b3942475a09bf692
- Source dataset
- uspto-grants-2015_10
- Patent number
- US09150555B2
Reaction notes
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