4-Bromo-2-fluorobenzaldehyde → (4-Bromo-2-fluorophenyl)(2-(diethoxymethyl)phenyl)methanol

Participants

Reaction Steps

To a mechanically stirred solution of 1-bromo-2-(diethoxymethyl)benzene (266 g) in dry diethyl ether (1.5 ) cooled to −70° C. under nitrogen was added a 2.5M solution of n-butyl lithium in hexanes (414 mL) dropwise over 30 min. The reaction mixture was stirred at a temperature less than −60° C. for 45 min then a solution of 4-bromo-2-fluorobenzaldehyde in dry diethyl ether (1.5 ) was added dropwise over 1 h maintaining the low temperature. The cooling bath was removed allowing the reaction to warm to +10° C. over 3 h. The reaction was quenched by the addition of water (500 mL). Organic layer was separated and the aqueous layer washed with ethyl acetate (2×500 mL). Combined organic layers were washed with brine then dried over anhydrous sodium sulfate and evaporated to yield the title product (371.1 g) as a yellow oil.

Provenance & Evidence