Dimethylformamide → Tert-butyl 3,5-difluoro-4-formylbenzoate
Reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[F:13][C:14]1[CH:15]=[C:16]([CH:24]=[C:25]([F:27])[CH:26]=1)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].CN([CH:31]=[O:32])C>C1COCC1.CCOC(C)=O.O.CC(O)=O>[F:13][C:14]1[CH:15]=[C:16]([CH:24]=[C:25]([F:27])[C:26]=1[CH:31]=[O:32])[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- -78 °C
Procedure
To a stirred solution of diisopropylamine (5 mL, 35.5 mmol, 1.2 eq) in THF (100 mL, anhyd) was slowly added BuLi (1.6M in hexanes, 20 mL, 32.3 mmol, 1.1 eq) at below 0° C. After addition was completed, the solution was cooled to −78° C. and then charged dropwise with a solution of tert-butyl 3,5-difluorobenzoate (6.3 g, 29 mmol) in THF (50 mL, anhyd) over 1 h. The resulting solution was stirred for another 2 h at −78° C. Next anhyd DMF (2.5 mL, 32.3 mmol, 1.1 eq) was added dropwise and, after 30 min, AcOH (4 mL) and water were added successively to quench the reaction. The reaction mixture was warmed to room temperature and diluted with EtOAc (100 mL). The organic layer was washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash column chromatography (Hex/EtOAc=4:1) to give tert-butyl 3,5-difluoro-4-formylbenzoate (5.8 g, 83%) as a white solid.
Workup
- customat below 0° C
- additionAfter addition
- customto quench
- customthe reaction
- temperatureThe reaction mixture was warmed to room temperature
- washThe organic layer was washed with brine
- dry with materialdried over MgSO4
- concentrationconcentrated in vacuo
- customThe residue was purified by flash column chromatography (Hex/EtOAc=4:1)
Sources & evidence
- ORD record
- ord-2ec4781141534797be24f6f4738975e9
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08846739B2
Reaction notes
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