Compound 1r

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Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

To a solution of 2-fluoro-5-(trifluoromethyl)benzaldehyde (S1; 1.92 g, 10.0 mmol) in DCM (10 mL) were added butylamine (1.04 mL, 10.5 mmol) and anhydrous MgSO₄ (1.0 g). The reaction was allowed to stir for 24 h at room temperature. Upon completion, the reaction mixture was filtered through Celite, concentrated in vacuo. The crude product (E)-N-butyl-1-(2-fluoro-5-(trifluoromethyl)phenyl)methanimine (S2)was used in the next step without further purification.To a solution of S2 (max. 10.0 mmol) in THF (15 mL) was added the corresponding Grignard reagent (20.0 mmol, 3.0 M in diethyl ether) dropwise at 0 °C. The reaction mixture was slowly warmed to room temperature, and stirred for 24 h. Upon completion, the reaction was quenched with 1 M HCl (aq) at 0 °C, and stirred for 30 min. The layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous MgSO₄, filtered and concentrated in vacuo. The crude residue was purified by flash chromatography to afford the desired product 1r as pale yellow oil.