Dimethylformamide → 2,3-Dichloro-6-fluorobenzaldehyde

Participants

Reaction Conditions

Reaction Steps

A solution of 1.3M s-butyl lithium in cyclohexane (244 mL, 317 mmol) is added to a dry-ice/acetone cooled solution of TMEDA (34 g, 293 mmol) in THF (250 mL), maintaining the internal reaction temperature <-70° C. The resulting reaction mixture is cooled and maintained at ≤-90° C. with an ether/liquid nitrogen bath while a solution of 1,2-dichloro-4-fluorobenzene (40 g, 244 mmol) in THF (100 mL) is added dropwise. The resulting reaction mixture is stirred with dry-ice/acetone cooling for 1h, then is cannulated into an ether/liquid nitrogen cooled and mechanically stirred solution of DMF (89.1 g, 1.22 mol) in THF (125 mL). The resulting mixture is warmed to -45° C. and partitioned between dilute aqueous HCl and ether. The organic solution is washed with aqueous NaHCO3, dried (MgSO4), and concentrated to afford 44.38 g of 2-fluoro-5,6-dichlorobenzaldehyde as an oil.

Provenance & Evidence