Chloride → Tert-butyl 3-bromo-5-(2,2-difluoro-1-hydroxyethyl)benzoate

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Reaction Steps

To a solution of tert-butyl 3,5-dibromobenzoate (18.43 g, 54.9 mmol) in tetrahydrofuran (137 mL) at 0° C. was added isopropylmagnessium chloride (2.0 M in THF; 46.6 mL, 93 mmol). The reaction mixture was warmed to ambient temperature. The reaction was monitor by LC-MS for disappearance of tert-butyl 3,5-dibromobenzoate. The mixture was cooled back to 0° C. and ethyl difluoroacetate (13.7 mL, 137 mmol) was added. The mixture was stirred at 0° C. for 1 h, then warmed to ambient temperature. After 18 h, methanol and saturated ammonium chloride were added and the mixture was concentrated to remove organic solvents. Water was added and the mixture was extracted with dichloromethane (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→75% hexanes/ethyl acetate) gave the title compound (4.04 g).

Provenance & Evidence