3-Bromoanisole → 2-((Dimethylamino)methyl)-1-(3-methoxyphenyl)cyclohexanol

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Reaction Steps

To 230 mL of anhydrous tetrahydrofuran (THF) cooled to −60° C. was added 9.36 g of n-butyl lithium (0.123 mol, 10 M solution in hexanes). The resulting yellow solution was stirred for 10 min and then 23.06 g of neat 3-bromoanisole (0.34 mol) was added dropwise with stirring. The resulting white suspension was stirred for 15 min. To the white suspension was then added dropwise, over a 4 hour period, a solution of 19.14 g of (±) 2-((dimethylamino)methyl)cyclohexanone (0.123 mol) and 400 mg of iron (III) chloride (2.5 mmol, 2 mol percent) in 190 mL of anhydrous THF at −60° C. The resulting reaction mixture was quenched with water, the organic phase was separated, the aqueous phase was extracted twice with diethyl ether and the diethyl ether extracts were combined. The combined ether extracts were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure to provide 37.77 g (0.084 mol, 68% yield) of the above-titled mixture in a ratio of 91.9:8.1 as determined using HPLC.

Provenance & Evidence