Acetic Acid → 3-Chloro-2-fluoro-6-methoxybenzaldehyde
Reaction equation
[Cl: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>[Cl: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-chloro-3-fluoroanisole (10.2 g, 63.5 mmol, Oakwood) in tetrahydrofuran (100 mL) at −78° C. was added lithium diisopropyl amine (42.3 mL, 1.8 M in THF, 76.2 mmol) dropwise during a period of 15 min. The mixture was stirred at −78° C. for another 20 mins. Then N,N-dimethyl-formamide (5.9 mL, 76.2 mmol) was added in one portion. The mixture was stirred at −78° C. for 10 min, then quenched with acetic acid (15.6 g, 254 mmol) and followed by the addition of water (80 mL). The mixture was partitioned between ethyl acetate and water. The organic layer was separated, concentrated to give 3-chloro-2-fluoro-6-methoxy-benzaldehyde as a yellow solid (Yield: 10 g, 85%)
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
Sources & evidence
- ORD record
- ord-48e648302af648bd8c1c2e8bed33d01d
- Source dataset
- uspto-grants-2012_03
- Patent number
- US08134001B2
Reaction notes
Loading…