Acetic Acid → 3-Bromo-2-fluoro-6-methoxybenzaldehyde
Reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[F:10].C(NC(C)C)(C)C.[Li].CN(C)[CH:21]=[O:22].C(O)(=O)C>O1CCCC1.O>[Br:1][C:2]1[C:3]([F:10])=[C:4]([C:5]([O:8][CH3:9])=[CH:6][CH:7]=1)[CH:21]=[O:22]Participants
7
Conditions
- Temperature
- -78 °C
Procedure
To a solution of 4-bromo-3-fluoroanisole (10 g, 48.7 mmol, Matrix) in tetrahydrofuran (100 mL) at −78° C. was added lithium diisopropyl amine (32.5 mL, 1.8 M in THF, 58.4 mmol) dropwise during a period of 15 min. The mixture was stirred at −78° C. for another 20 mins. Then N,N-dimethyl-formamide (4.53 mL, 58.4 mmol) was added in one portion. The mixture was stirred at −78° C. for 10 min, then quenched with acetic acid (12 g, 194 mmol) and followed by the addition of water (61 mL). The mixture was partitioned between ethyl acetate and water. The organic layer was separated, concentrated. The residue was purified by chromatography (EtOAc:hexanes=1:4) to give 3-bromo-2-fluoro-6-methoxy-benzaldehyde as a yellow solid (Yield: 10 g, 89%)
Workup
- stirringThe mixture was stirred at −78° C. for 10 min
- customThe mixture was partitioned between ethyl acetate and water
- customThe organic layer was separated
- concentrationconcentrated
- customThe residue was purified by chromatography (EtOAc:hexanes=1:4)
Sources & evidence
- ORD record
- ord-f6d740b1e3b34751afb97d2e9fdbdb75
- Source dataset
- uspto-grants-2012_03
- Patent number
- US08134001B2
Reaction notes
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