Diisopropylamine → tert-Butyl 1-(3-bromo-4-chlorobenzyl)cyclopropanecarboxylate

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Reaction Conditions

Reaction Steps

Under argon, 140.2 ml (1.0 mol) of diisopropylamine were dissolved in 1200 ml of dry THF, and the mixture was cooled to −30° C. 400 ml (1.0 mol) of n-butyllithium solution (2.5 M in hexane) were added dropwise. The resulting mixture was warmed to 0° C. and then cooled to −70° C. A solution of 94.8 g (0.667 mol) of tert-butyl cyclopropanecarboxylate in 750 ml of THF was added to the reaction solution, and during the addition the temperature was kept below −60° C. After 4 h of stirring at −60° C., a solution of 208.6 g (0.733 mol) of 2-bromo-4-(bromomethyl)-1-chlorobenzene in 550 ml of THF was added, and once more the temperature was kept below −60° C. during the addition. The reaction mixture was slowly warmed to RT overnight, and saturated aqueous ammonium chloride solution was then added carefully. After phase separation, the aqueous phase was extracted 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/dichloromethane 4:1). This gave 95.5 g (41.4% of theory) of the title compound.

Provenance & Evidence