5-BROMO-2-FLUORO-3-METHYLBENZALDEHYDE synthesis

Yield:-

Reaction Conditions:

with hydrogenchloride;n-butyllithium in tetrahydrofuran;hexane;N,N-dimethyl-formamide

Steps:

96.1 Step 1.
Step 1.
5-Bromo-2-fluoro-3-methylbenzaldehyde
To a stirred solution of di-isopropyl amine (4.01 g, 39.88 mmol) in THF (20 mL) was added n-BuLi (1.6 M in hexane) (19.9 mL, 31.91 mmol) at -78° C. slowly dropwise over the period of 10 min, the reaction mixture was stirred at -78° C. for 30 min.
A solution of 4-bromo-1-fluoro-2-methylbenzene (5.0 g, 26.6 mmol) in THF (30.0 mL) was added at -78° C., and the reaction mixture was stirred for 1 h at the same temperature. DMF (5.0 mL) was added and stirred at -78° C. for another 30 min.
The reaction was monitored by TLC; then the reaction mixture was quenched with 1N HCl solution (aq) at 0° C.
The aqueous layer was extracted with Et₂O, washed with water and saturated brine solution.
The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to obtain the crude compound purified by flash column chromatography (SiO₂, 100-200 mesh; eluting with 5% EtOAc/pet ether) to afford the title compound as a white solid (3.6 g, 64%); mp 48-50° C.: ¹H NMR (400 MHz, CDCl₃) δ 8.33 (s, 1H), 8.22 (s, 1H), 7.67 (s, 1H), 7.60 (s, 1H), 6.75 (dd, J=17.6, 10.8 Hz, 1H), 5.92 (dd, J=17.6, 10.8 Hz, 1H), 5.52 (d, J=17.6 Hz, 1H), 2.21 (s, 3H); ESIMS m/z 211.35 ([M-H]^-).

References:

Dow AgroSciences LLC;Lo, William C.;Hunter, James E.;Watson, Gerald B.;Patny, Akshay;Iyer, Pravin S.;Boruwa, Joshodeep US2014/171314, 2014, A1 Location in patent:Page/Page column