Hydrochloric Acid → 4-(3-Bromo-4-formyl-phenoxy)-3-fluoro-benzonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-fluoro-4-hydroxy-benzonitrile (5 g, 36 mmol) in DMF (anhydrous, 100 mL) was slowly added K2CO3 (5.54 g, 40.1 mmol). After stirring for 5 minutes, to the solution was added 2-bromo-4-fluoro-benzaldehyde (8.89 g, 43.8 mmol). The reaction was heated at 70° C. and monitored by T.L.C. After 4 hours, the heating was stopped and after cooling to the room temperature, 100 mL of EtOAc was added. With stirring, 1 M HCl (˜50 mL) was slowly added until the pH was 7. The organic layer was then washed with H2O (3×50 mL), dried over MgSO4 and filtered. The filtrate was evaporated under vacuum. The residue was purified over silica gel, eluting with 12.5% EtOAc/hexanes to afford 4-(3-bromo-4-formyl-phenoxy)-3-fluoro-benzonitrile (3) 7.1 g in 61% yield. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 10.28 (s, 1 H), 7.96 (d, J=8.60 Hz, 1 H), 7.51-7.59 (m, 2 H), 7.21-7.29 (m, 3 H), 7.03 (dd, 1 H).

Provenance & Evidence