1-Piperidinecarboxaldehyde → 4-Phenylpyridine-2-carboxaldehyde
Reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.[Li]CCCC.N1([CH:25]=[O:26])CCCCC1.[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[C:8]1([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([CH:25]=[O:26])[CH:7]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1Participants
Conditions
- Temperature
- -78 °C
Procedure
A cooled (−78° C.) solution of commercially available 2-bromo-4-phenylpyridine (500 mg; 2.13 mmol) in anh. THF (9 ml) was treated dropwise with a solution of 1.6 M n-BuLi in hexanes (1.33 ml; 2.13 mmol), and the resulting mixture was further stirred at −78° C., under nitrogen, for 1 h. Commercially available piperidine-1-carbaldehyde (483 mg; 4.27 mmol) was added dropwise to the cooled (−78° C.) reaction mixture, and stirring was continued at −78° C. for 15 min., and then at 0° C. for 1 h. Aq. sat. NH4Cl (25 ml) and AcOEt (50 ml) were added, and the separated organic layer was further washed with brine (20 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (toluene/AcOEt=7/3) afforded 4-phenylpicolinaldehyde as a yellow solid. LC-MS (conditions A): tR=0.43 min.; [M+H]+: 184.48 g/mol.
Workup
- temperaturecooled
- custom(−78° C.) reaction mixture
- stirringstirring
- waitwas continued at −78° C. for 15 min.
- waitat 0° C. for 1 h
- washthe separated organic layer was further washed with brine (20 ml)
- dry with materialdried over anh. MgSO4
- filtrationfiltered
- concentrationconcentrated to dryness under reduced pressure
- customPurification by FC (toluene/AcOEt=7/3)
Sources & evidence
- ORD record
- ord-91965e64d04c40d4b257646bbeddf5e0
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09242970B2
Reaction notes
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