Hydrochloric Acid → 4-Bromo-2-chlorobenzaldehyde

Participants

Reaction Conditions

Reaction Steps

To 4-bromo-2-chlorobenzonitrile (2.0 g, 9.2 mmol) in toluene (50 mL) at −78° C. under argon was added DIBAL (1M solution in toluene, 13.9 mL, 13.9 mmol). The mixture was allowed to warm to −50° C. over 4 h. MeOH (4.5 mL) and water (4.5 mL) were added and the mixture stirred for 10 min at −50° C. The mixture was allowed to warm to rt, acidified with 2N HCl (pH<7) and extracted with EtOAc (200 mL) and water (100 mL). The aqueous was further extracted with EtOAc (2×50 mL), the combined organics were then washed with brine and dried (MgSO4). The solvent was removed in vacuo and the residue purified by column chromatography (25% DCM: Iso-hexane) to give 4-bromo-2-chlorobenzaldehyde. To a solution of 4-bromo-2-chlorobenzaldehyde (750 mg, 3.4 mmol) in DME (22 mL) and EtOH (15 mL) was added 3-carboxamidobenzene boronic acid (676 mg, 4.1 mmol) and 2M Na2CO3 solution (15 mL). Argon was bubbled through the mixture for 15 min. Bis(triphenylphosphino) palladium dichloride (120 mg, 0.17 mmol) was added and the reaction heated to 75° C. for 6.5 h before cooling to rt. The mixture was partitioned between water (200 mL) and EtOAc (200 mL), the aqueous was extracted with EtOAc (2×50 mL) and the combined organics dried (MgSO4). The solvent was removed in vacuo and the residue purified by column chromatography (50% EtOAc: Iso-hexane to 100% EtOAc) to give the title compound: RT=3.19 min; m/z (ES+)=301.0 [M+H+MeCN]+.

Provenance & Evidence