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

Temperature

-30 °C

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.

1. temperaturethe resulting mixture was warmed to 0° C.
2. temperaturecooled to −70° C
3. custombeing kept below −60° C
4. customwas once more kept below −60° C
5. temperatureThe reaction mixture was then slowly warmed to RT overnight
6. customAfter phase separation
7. extractionthe aqueous phase was extracted twice with ethyl acetate
8. dry with materialThe combined organic phases were dried over magnesium sulphate
9. concentrationconcentrated under reduced pressure
10. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 100:1)

ORD record

ord-febae51a89114ea6a3c4427d7f8c7da7

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09018414B2