The general procedure for the synthesis of 2-chloro-4-(trifluoromethyl)benzaldehyde from 2-chloro-4-(trifluoromethyl)benzonitrile was as follows: first, 2-chloro-4-(trifluoromethyl)benzenecarbonitrile (500 mg, 2.43 mmol) was dissolved in toluene (3 mL), and cooled to -78 °C under nitrogen protection. Subsequently, diisobutylaluminum hydride (DIBAL-H, 4865 μL, 4.86 mmol) was slowly added dropwise and the reaction was stirred for 1 hour at this temperature. Upon completion of the reaction, the mixture was slowly warmed to 0 °C and the reaction was quenched by the addition of acetic acid (2 mL) followed by the addition of water (10 mL). After continued stirring for 2 hours, the reaction mixture was extracted twice with ethyl acetate. The organic phases were combined, washed with Rochelle's salt solution, dried over anhydrous magnesium sulfate, filtered and concentrated. Finally, purification by Biotage 25 column chromatography using gradient elution (100% hexane to 20% dichloromethane/hexane) afforded 2-chloro-4-(trifluoromethyl)benzaldehyde (400 mg, 1.92 mmol, 78.8% yield) as a clear oil.
