Dimethylformamide → 2-Bromo-3-chloro-6-fluorobenzaldehyde
Reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[Br:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[Cl:21].CN([CH:25]=[O:26])C>C1COCC1.O>[Br:13][C:14]1[C:15]([Cl:21])=[CH:16][CH:17]=[C:18]([F:20])[C:19]=1[CH:25]=[O:26]Participants
Conditions
- Temperature
- -75 °C
Procedure
To a solution of diisopropylamine (5 mL, 35.4 mmol) in THF (30 mL) at 0° C. under argon was added n-butyl lithium (16.5 mL of 1.6 M solution in hexane, 26.4 mmol) slowly over 20 minutes. The mixture was cooled to −75° C. and 2-bromo-1-chloro-4-fluorobenzene (5 g, 23.9 mmol) in THF (20 mL) was added dropwise over 15 mins whilst maintaining the temperature <−70° C. The solution was then stirred at −75° C. for 45 mins and then DMF (2.2 mL, 28.6 mmol) was added over 5 mins. The mixture was stirred at −78° C. for 2 hrs and then allowed to reach room temperature. Water was added and the aqueous layer was extracted with ethyl acetate. The combined extracts were washed with brine and the solvent evaporated. Chromatography (silica gel, ethyl acetate/hexane) gave the title compound (D21) as a yellow solid (3.344 g)
Workup
- temperaturewhilst maintaining the temperature <−70° C
- stirringThe mixture was stirred at −78° C. for 2 hrs
- customto reach room temperature
- extractionthe aqueous layer was extracted with ethyl acetate
- washThe combined extracts were washed with brine
- customthe solvent evaporated
Sources & evidence
- ORD record
- ord-7284bce253ed4c6c9d3e4ae04b4f575c
- Source dataset
- uspto-grants-2011_06
- Patent number
- US07960563B2
Reaction notes
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