Tetrahydrofuran → tert-Butyl (2-chloro-4-formylpyridin-3-yl)carbamate
Reaction equation
[Cl:1][C:2]1[C:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:6][CH:5]=[CH:4][N:3]=1.CN(CCN(C)C)C.C([Li])CCC.[NH4+].[Cl-].C1C[O:34][CH2:33]C1>CCCCCC.CCOC(C)=O.CN(C=O)C>[Cl:1][C:2]1[C:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[C:6]([CH:33]=[O:34])[CH:5]=[CH:4][N:3]=1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- -10 °C
Procedure
To a solution of tert-butyl (2-chloropyridin-3-yl)carbamate (7-2) (3.01 g, 13.2 mmol) and TMEDA (3.37 g, 29 mmol) in THF (50 mL) at −78° C. was added a 2.5 M solution of n-butyllithium in hexane (11.6 mL) dropwise over 10 minutes and the mixture was stirred for 1 hour. The mixture was warmed up to −10° C. and then cooled to −78° C. DMF (3.06 mL) was added to the mixture and then the mixture was warmed to ambient temperature over 3 hours. Saturated aq. NH4Cl and EtOAc were added to the mixture and the organic layer was washed with H2O and brine, dried over MgSO4, filtered, concentrated in vacuo, and purified by silica gel chromatography (0-80% EtOAc/hexane) to give tert-butyl (2-chloro-4-formylpyridin-3-yl)carbamate (7-3) as a yellow solid.
Workup
- temperaturecooled to −78° C
- temperaturethe mixture was warmed to ambient temperature over 3 hours
- washthe organic layer was washed with H2O and brine
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- custompurified by silica gel chromatography (0-80% EtOAc/hexane)
Sources & evidence
- ORD record
- ord-842791954b584bc2b78e77663e4a401e
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08614221B2
Reaction notes
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