Diisopropylamine → tert-Butyl 1-(3-bromobenzyl)cyclopropanecarboxylate

Temperature

-40 °C

Under argon, 14.8 ml (105.48 mmol) of diisopropylamine were initially charged in 66 ml of dry THF, and the mixture was cooled to −40° C. 42.2 ml (105.48 mmol) of n-butyllithium solution (2.5 M in hexane) were slowly added dropwise, and the mixture was stirred for 30 min. The reaction solution was then cooled to −78° C., and a solution of 10.0 g (70.32 mmol) of tert-butyl cyclopropanecarboxylate in 17 ml of THF were added. After 4 h of stirring at −78° C., a solution of 19.34 g (77.36 mmol) of 3-bromobenzyl bromide in 17 ml of THF was added. Slowly, the reaction mixture was warmed to RT overnight, ammonium chloride solution was then added carefully and the mixture was extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. The crude product was purified by chromatography on 750 g of silica gel (mobile phase cyclohexane/dichloromethane 50:1, then 5:1). This gave 13.3 g (60.7% of theory) of the title compound.

1. temperatureThe reaction solution was then cooled to −78° C.
2. stirringAfter 4 h of stirring at −78° C.
3. temperatureSlowly, the reaction mixture was warmed to RT overnight
4. extractionthe mixture was extracted three times with ethyl acetate
5. washThe combined organic phases were washed with saturated sodium chloride solution
6. dry with materialdried over magnesium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe crude product was purified by chromatography on 750 g of silica gel (mobile phase cyclohexane/dichloromethane 50:1

ORD record

ord-7f8f30805a814b1c9f1edd263ead40ae

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987256B2