Diisopropylamine → (+/-)-Tert-butyl 2-(3-bromo-4-chlorobenzyl)-2-methylbutanoate

Participants

Reaction Conditions

Reaction Steps

Under argon, 5.8 ml (41.6 mmol) of diisopropylamine were dissolved in 50 ml of dry THF, and the mixture was cooled to −30° C. 16.6 ml (41.6 mmol) of n-butyllithium solution (2.5 M in hexane) were added dropwise, and the resulting mixture was warmed to 0° C. and then cooled to −70° C. A solution of 5.06 g (32.0 mmol) of tert-butyl 2-methylbutanoate in 20 ml of THF was added, the reaction temperature being kept below −60° C. After 4 h of stirring at −60° C., a solution of 10.0 g (35.2 mmol) of 2-bromo-4-(bromomethyl)-1-chlorobenzene in 30 ml of THF was added, and the temperature was once more kept below −60° C. The reaction mixture was then slowly warmed to RT overnight, and saturated aqueous ammonium chloride solution and ethyl acetate were then added. After phase separation, the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 100:1). This gave 7.62 g (65.9% of theory) of the title compound.

Provenance & Evidence