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

Participants

Reaction Conditions

Reaction Steps

To a solution of 3.53 g of (±)-2-((dimethylamino)methyl)cyclohexanone (23 mmol) dissolved in 20 mL of THF at 0° C. was added dropwise a solution of 37 mg of iron (III) chloride (0.2 mmol, 1 mol percent) in 3 mL of THF at 0° C. The resulting violet solution was cooled to −78° C. In a separate vessel, 5.10 g of 3-bromoanisole (27 mmol) was dissolved in 50 mL of THF and the resulting solution was cooled to −78° C. To the solution of 3-bromoanisole was added dropwise with stirring 2.07 g of n-butyl lithium (27 mmol, 10 M solution in hexanes). The resulting white suspension was stirred for 1 hour and then transferred dropwise over a 4 hour period to the solution of (±) 2-((dimethylamino)methyl) cyclohexanone and iron (III) chloride at −78° C. The reaction mixture was quenched with water, the organic phase was separated, the aqueous phase was extracted three times 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 6.92 g (14 mmol, 62% yield) of the above-titled mixture in a ratio of 97.8:2.2 as determined using HPLC.

Provenance & Evidence