Dimethylformamide → N-(2-Fluoro-6-formylphenyl)pivalamide
Reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12].C([Li])CCC.CN(C)[CH:23]=[O:24]>O1CCCC1>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH:23]=[O:24])[C:3]=1[NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
N-(2-Bromo-6-fluorophenyl)pivalamide (7.0 g, 25.5 mmol) was dissolved in tetrahydrofuran (200 mL). The mixture was cooled to −78° C., and treated with butyllithium (2 M in cyclohexane, 31.0 mL, 62.0 mmol) dropwise. The reaction mixture was held at −78° C. for 30 minutes. A solution of N,N-dimethylformamide (10.0 mL, 129 mmol) in tetrahydrofuran (30 mL) was added to the reaction mixture dropwise. The reaction was held at −78° C. for 30 minutes and quenched by the addition of aqueous ammonium chloride. The mixture was allowed to warm to room temperature and extracted with ethyl acetate (2×). The combined organic layers were dried (magnesium sulfate), filtered, and concentrated. Silica gel chromatography afforded the desired product as white solid in 80% yield. 1H NMR (300 MHz, CDCl3): δ 9.93 (d, J=1.83, 1H), 9.14 (bs, 1H), 7.56-7.50 (m, 1H), 7.42-7.25 (m, 2H), 1.34 (s, 9H). Mass spec.: 224.2 (MH)+.
Workup
- waitThe reaction was held at −78° C. for 30 minutes
- customquenched by the addition of aqueous ammonium chloride
- temperatureto warm to room temperature
- extractionextracted with ethyl acetate (2×)
- dry with materialThe combined organic layers were dried (magnesium sulfate)
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-7fe60865bdd249c4b37c6dbae59be1f9
- Source dataset
- uspto-grants-2010_08
- Patent number
- US07772244B2
Reaction notes
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