Dimethylformamide → 2-Bromo-6-fluorobenzaldehyde

Participants

Reaction Conditions

Reaction Steps

A solution of n-butyllithium (2.5M in hexanes, 2.866 L, 7.17 mol) is added dropwise to a stirred solution of diisopropylamine (745.7 g, 7.37 mol) in tetrahydrofuran (1.630 L) such that the temperature is maintained in the range −60 to −78° C. The resulting suspension is stirred for 1.5 h at −75 to −78° C. A solution of 1-bromo-3-fluorobenzene (1.228 Kg, 7.02 mol) in tetrahydrofuran (2.40 L) is added slowly to the reaction mixture over 1.5 h. Stirring is continued for 30 min at −70 to −71° C. Dimethylformamide (511.3 g) is added over 1 h. The reaction mixture is allowed to warm to −15° C. and is quenched by the slow addition of acetic acid (1.965 L) over 20 min. TBME (5.20 L) and water (6.25 L) are added. The resultant solution is stirred vigorously and the layers are separated. The aqueous layer is extracted with TBME (1.965 L) twice and the combined organic layers are washed with 0.2 M hydrochloric acid (2×5.00 L), saturated aqueous sodium hydrogen carbonate solution (2×2.50 L) and water (3.50 L). The organic layer is dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford the title compound as a yellow crystalline solid (1.367 Kg, 96%). 1H NMR (CDCl3): δ 10.36 (s, 1H), 7.49 (d, 1H, 3=7.8 Hz), 7.45-7.37 (m, 1H), 7.15 (t, 1H, J=7.9 Hz).

Provenance & Evidence