Diisopropylamine → 4-Tert-butyl 1-methyl 2-(4-chlorobenzyl)succinate

Temperature

0 °C

BuLi (5.2 mL, 1.6M in hexanes) was added to a 0° C. solution of diisopropylamine (0.91 g, 9.0 mmol) in THF (40 mL). The reaction mixture was then stirred at 0° C. for 30 minutes, and then cooled to −78° C. A solution of methyl 3-(4-chlorophenyl)propanoate (1.5 g, 7.5 mmol) in THF (8 mL) was added slowly, and the reaction mixture was stirred at −78° C. for 40 minutes. A solution tert-butyl 2-bromoacetate (4.4 g, 22.7 mmol) in THF (5 mL) was then added. The reaction was then stirred for 30 minutes at −78° C. and then warmed to room temperature and stirred overnight. The reaction was then quenched with saturated NH4Cl and concentrated to remove THF. The reaction was then extracted with EtOAc, and the combined extracts were dried (Na2SO4), filtered, concentrated, and dried in vacuo to give 4-tert-butyl 1-methyl 2-(4-chlorobenzyl)succinate (1.91 g, 81%) as an oil.

1. temperaturecooled to −78° C
2. stirringthe reaction mixture was stirred at −78° C. for 40 minutes
3. stirringThe reaction was then stirred for 30 minutes at −78° C.
4. temperaturewarmed to room temperature
5. stirringstirred overnight
6. customThe reaction was then quenched with saturated NH4Cl
7. concentrationconcentrated
8. customto remove THF
9. extractionThe reaction was then extracted with EtOAc
10. dry with materialthe combined extracts were dried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated
13. customdried in vacuo

ORD record

ord-46182d0ac5b349cb97b46fdf29c5843d

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08372842B2