3-Bromo-2-fluorobenzaldehyde → (3-Bromo-2-fluorophenyl)(5-fluoro-2-methoxyphenyl)methanol

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-bromo-2-fluorobenzaldehyde (1.0 g, 4.93 mmol) in THF (21.42 mL) cooled to −78° C. was added (5-fluoro-2-methoxyphenyl)magnesium bromide in THF (11.82 mL, 5.91 mmol). The reaction mixture was maintained at −78° C. for at least 1 hr, then allowed to warm to room temperature. The reaction mixture was then re-cooled to 0° C. and additional (5-fluoro-2-methoxyphenyl) magnesium bromide in THF (11.82 mL, 5.91 mmol) was added. The reaction mixture was allowed to warm to room temperature overnight. The reaction was quenched with a saturated aqueous solution of NH4Cl and diluted with CH2Cl2. The layers were separated and the aqueous phase was extracted with CH2Cl2 (2×). Organics combined, dried over Na2SO4, filtered, and concentrated to afford a yellow residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (80 g column, 60 mL/min, 0-30% EtOAc in hexanes over 20 min, tr=17.5 min) gave the title compound (1.62 g, 4.92 mmol, 100% yield) as a colorless liquid.

Provenance & Evidence