Methanol → Methyl 2-(2,5-dichloro-4-hydroxyphenyl)acetate

Participants

Reaction Steps

Boron tribromide (1.581 mL, 16.72 mmol) was added dropwise to 2-(2,5-dichloro-4-methoxyphenyl)acetic acid (Intermediate 4-4; 655 mg, 2.79 mmol) in dichloromethane (20 mL) at ambient temperature under nitrogen. The resulting solution was stirred at ambient temperature for 60 minutes. The reaction mixture was cautiously added to methanol (100 mL) (—care reaction is vigorous and exothermic—mixture became reasonably warm during the addition) and the mixture was stirred for a further 2 hours at ambient temperature. The reaction mixture was evaporated to dryness and redissolved in DCM (100 mL), and washed sequentially with 2M HCl (50 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 2-(2,5-dichloro-4-hydroxyphenyl)acetate (258 mg, 39.4%) as a pale yellow solid.

Provenance & Evidence