[Synthesis]
Under argon protection, 2-bromo-5-fluorotoluene (20 g) was dissolved in anhydrous tetrahydrofuran (200 ml) and cooled to -78 °C. Lithium diisopropylammonium (2.0 M, heptane-tetrahydrofuran-ethylbenzene solution, 52.9 ml) was added slowly and dropwise. After keeping the reaction stirred at -78 °C for 2 h, anhydrous tetrahydrofuran (50 ml) solution of N,N-dimethylformamide (41 ml) was added dropwise. The reaction system was gradually warmed up to room temperature and stirring was continued for 1 hour. After completion of the reaction, the reaction was quenched by the addition of water and the pH was adjusted to neutral with 1N hydrochloric acid. The reaction mixture was extracted with ethyl acetate, the organic phases were combined, washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was removed by concentration under reduced pressure, and the crude product obtained was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=24:1), and then recrystallized with hexane-ethyl acetate mixed solvent to obtain 5-bromo-2-fluoro-4-methylbenzaldehyde (9.39 g) as a white solid. The product was confirmed by 1H-NMR (200 MHz, CDCl3): δ2.47 (3H, s), 7.09 (1H, d, J=8.6 Hz), 8.09 (1H, d, J=6.6 Hz), 10.25 (1H, s). The results of elemental analysis are consistent with the theoretical values (C8H6OBrF calculated values: C, 44.27; H, 2.79; measured values: C, 44.29; H, 2.79). |