1-Bromo-4-methoxy-2-methylbenzene → (2-Fluoro-4-methoxyphenyl)(4-methoxy-2-methylphenyl)methanol

Participants

Reaction Conditions

Reaction Steps

n-Butyllithium (2.5 M, 44.0 mL) was added dropwise into a cold (−78° C.) solution of 1-bromo-4-methoxy-2-methylbenzene (22.0 g, 109.4 mmol), and THF (150 mL). The reaction mixture was stirred at −78° C. for 3 h, and then 2-fluoro-4-methoxybenzaldehyde (16.8 g, 109.4 mmol) in THF (10 mL) was added. The mixture was allowed to warm up to 0° C. stirred for 10 min, and then quenched with aqueous ammonium chloride. The mixture was poured into water, acidified with HCl (2N) and extracted with EtOAc. The organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography (hexanes/EtOAc 3/1) gave (2-fluoro-4-methoxyphenyl)(4-methoxy-2-methylphenyl)methanol as a yellow oil (23.6 g, 78% yield). The product was dissolved in acetone (150 mL), cooled to 10° C. and Jones Reagent (79.7 mL) was added dropwise. The reaction stirred for poured into water and extracted with ethyl ether. The organic extracts were dried over MgSO4. Evaporation and purification by flash chromatography (hexanes/EtOAc 3/1) gave a yellow oil (23.6 g, 78% yield, m.p. 88-90° C.); MS m/e 275 (M+H)+.

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