3-Bromo-5-chlorobenzoic acid → (3-Bromo-5-chlorophenyl)methanol

Participants

Reaction Steps

To a solution of 3-bromo-5-chlorobenzoic acid (1.0 g, 4.3 mmol) in THF (30 mL) was added borane-THF solution (13 mL, 1.0 M) at 0° C. The mixture was allowed to stir for 16 hours. TLC showed clean conversion. The reaction was quenched with methanol, diluted with EtOAc (100 mL), washed with 0.5 N HCl, 0.5 N NaOH, and brine, dried over sodium sulfate, filtered and concentrated to give rise to (3-bromo-5-chlorophenyl)methanol as a waxy solid (680 mg, 72% yield). To the above solid (680 mg, 3.1 mmol) was added thallium trifluoroacetate (1.8 g, 3.4 mmol) and TFA (4 mL). The mixture was allowed to stir at RT for 16 hours. The volatiles were removed under reduced pressure. The residue was pumped under high vacuum for 15 minutes before palladium (II) chloride (0.054 g, 0.31 mmol), magnesium oxide (0.25 g, 6.1 mmol), lithium chloride (0.13 g, 0.31 mmol), and methanol (30 mL) were added. The mixture was stirred under an atmosphere of carbon mono-oxide until the reaction turned black. The reaction was diluted with DCM (50 mL), filtered through a pad of Celite®, adsorbed onto silica gel, and purified by MPLC. Removal of solvent gave rise to a mixture of 5-bromo-7-chloro-2-benzofuran-1(3H)-one and 7-bromo-5-chloro-2-benzofuran-1(3H)-one. LC/MS: (IE, m/z) (M+1)+=249.0;

Provenance & Evidence