Carbon Dioxide → (4-bromo-3,5-difluorophenyl)methanol

Participants

Reaction Conditions

Reaction Steps

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 4-bromo-3,5-difluoroiodobenzene (790 mg, 2.48 mmol) in dry Et2O (12 mL) was added to a n-BuLi (0.98 mL of a 2.5M solution in hexanes, 2.45 mmol) at −78° C. The reaction mixture was stirred at −78° C. for 2 h before solid CO2 was added. The reaction mixture was stirred at −78° C. for 10 min and then allowed to warm up to rt. The mixture was then diluted with EA and aq. 1N HCl was added. The layers separated and the org. layer dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the crude carboxylic acid as a pale yellow solid. The crude material (270 mg, 1.14 mmol) was dissolved in dry THF (6 mL) and treated with BH3.Me2S complex (1.0 M in THF, 2.3 mL, 2.30 mmol) at 0° C. The reaction mixture was then warmed to 50° C. and stirred at this temperature until completion of the reaction. The mixture was cooled to 0° C. and water was added followed by EA. The layers were separated and the aq. layer extracted with EA (3×). The combined org. extracts were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by FC (hept-EA 9:1 to 2:1) to give the title compound as a white solid. TLC:rf (1:1 EA-hept)=0.53.

Provenance & Evidence