Allyl bromide → (2S,4R)-1-tert-butyl 2-ethyl 4-allyl-5-oxopyrrolidine-1,2-dicarboxylate

Temperature

-78 °C

To a solution of HMDS in anhydrous THF (200 mL) was added dropwise 2.5 M n-BuLi in hexane (130 mL) and the mixture was stirred at −78° C. for 1 hr. To a solution of (S)-1-tert-butyl 2-ethyl 5-oxopyrrolidine-1,2-dicarboxylate (80 g, 0.311 mol) in anhydrous THF (1600 mL) stirred at −78° C. was added lithium hexamethyldisilazide in THF. After the reaction mixture was stirred at −78° C. for 1 hr, 3-bromopropene (38.47 g, 0.318 mol) in THF (200 mL) was added and stirring was continued for 2 hr. The reaction mixture was quenched with saturated ammonium chloride solution (600 mL) at −78° C. and extracted with EtOAc (3×500 mL). The combined organic layers were dried over Na2SO4, filtered and evaporated to dryness. The crude product was separated by column chromatography to afford (2S,4R)-1-tert-butyl 2-ethyl 4-allyl-5-oxopyrrolidine-1,2-dicarboxylate (15 g, 16%).

1. stirringAfter the reaction mixture was stirred at −78° C. for 1 hr
2. stirringstirring
3. waitwas continued for 2 hr
4. customThe reaction mixture was quenched with saturated ammonium chloride solution (600 mL) at −78° C.
5. extractionextracted with EtOAc (3×500 mL)
6. dry with materialThe combined organic layers were dried over Na2SO4
7. filtrationfiltered
8. customevaporated to dryness
9. customThe crude product was separated by column chromatography

ORD record

ord-80666c0c556a416f9c990878da7959a2

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08487108B2